Deforming element-included dispensing tip, deforming element-included dispensing device, and deforming element-included dispensing processing method

ABSTRACT

It is an object to provide a deforming element-included dispensing tip, a deforming element-included dispensing device, and a deforming element-included dispensing processing method not requiring any cylinder and capable of achieving highly precise position control and enhancing integration of higher density and reducing the burden in the quality control in reaction processing of a biological material for extraction of DNA and the like. 
     A tip-shaped container formed with a non-deforming wall having an opening portion at an upper side and an inlet unit at a lower side for allowing fluid to flow in and flow out and a sealing plug attached to the opening portion so as to seal the opening portion are provided, and the sealing plug is configured to be provided with a deforming element.

CROSS REFERENCE

This application is a continuation of U.S. patent application Ser. No.14/424,075, the 371(c) date for which is Feb. 26, 2015, and which is aUnited States national phase application of international patentapplication number PCT/JP2013/073513, filed Sep. 2, 2013, which claimspriority to Japanese patent application number 2012-192519, filed Aug.31, 2012, and to Japanese patent application number 2013-126057, filedJun. 14, 2013, the entire disclosures of which are hereby incorporatedherein by reference.

TECHNICAL FIELD

The present invention relates to a deforming element-included dispensingtip, a deforming element-included dispensing device, and a deformingelement-included dispensing processing method.

BACKGROUND ART

There is a dispensing device of which patent application was filed bythe applicant of the present application and matured into a patent. Inthe dispensing device, a dispensing tip engages with and attaches to alower end portion of a nozzle at an attachment opening portion, and aplunger in a cylinder in communication with the nozzle is caused toslide, so that a liquid is sucked or discharged through the lower endthereof into and out of the dispensing tip (Patent Literatures 1 to 4).

However, mechanisms such as a cylinder and a plunger used in thedispensing device are highly precisely processed components such as asyringe, and in particular, the change in the volume in the cylinder isbasically integral with the change in the volume in the dispensing tip,and it is necessary to transmit it to a joint portion between theplunger and a driving device of the plunger without any looseness. Thesucking and discharging mechanism thereof, the dispensing tip, and thelike are engaged without any leakage of gas or liquid. For this reason,a high degree of quality control may be required. More specifically, inorder to engage the nozzle of the sucking and discharging mechanism withthe attachment opening portion of the dispensing tip without any leakageof fluid, a high load is imposed on the dispensing tip when the nozzleis attached because of the existence of an O ring and the like providedon the attachment opening portion, and, e.g., this may destroy thedispensing tip and may cause abrasion of the nozzle, and therefore, itis necessary to exchange the nozzle and processing with a high degree ofaccuracy. In order to control the sucking and discharging of thedispensing tip, a cylinder having a volume corresponding to the volumeof the dispensing tip is necessary, and therefore, there is a problem inthat the size of the device increases when a large volume of liquid istreated.

On the other hand, in the past, a pipette has been known, which issurrounded by a wall surface such as rubber and is capable ofaccommodating liquid and gas therein, wherein the pipette deforms whenthe wall surface is manually pressed, so that the pipette sucks anddischarges liquid. However, since this pipette is manually handled, asingle user can handle up to only a single pipette, and it is impossibleto perform processing at a time using many pipettes. The deforming ofthe pipette is different according to the magnitude of the force, thedirection of the force, and the position where the force is applied, andtherefore, in the manual pipette operation, it is difficult to performprocessing that is precise in terms of amount and perform repetitionwith a high degree of reproducibility.

As a method of improving this, the applicant of the present applicationhas developed a device using a deforming-type dispensing tip in which adeforming wall surface forms a portion of a wall surface accommodatingliquid and gas, and the device sucks and discharges liquid by deformingthe deforming wall surface (WO 2007/081000). In the device using thisdeforming-type dispensing tip, gas is accommodated in an accommodationunit partially formed with the deforming wall surface that deforms, andtherefore, it may be necessary to rigidity hold an inlet unit connectedto an accommodation unit partially having the deforming wall surface sothat it does not deviate.

Further, in order to deform the deforming-type dispensing tip asintended, it may be necessary to loosely insert the deforming-typedispensing tip into a holder and the like and use it so that thedeforming wall surface deforms only in a predetermined direction.

The deforming wall surface is used for a portion of an external wall ofthe deforming-type dispensing tip, and there is a problem in that it maybe deformed or damaged, and this may increase the burden in the qualitycontrol.

It should be noted that there is a method of directly transferring froma container to a container without using any dispensing tip. Althoughthis method simplifies the device structure, a person is required, andthere is a risk of contamination because of a contact between acontainer and a container, and there is a problem in that a high degreeof reliability cannot be obtained.

CITATION LIST Patent Literature

Patent Literature 1: JP 3115501 B1

Patent Literature 2: JP 3739953 B1

Patent Literature 3: JP 3630497 B1

Patent Literature 4: JP 3682302 B1

Patent Literature 5: WO 2007/081000 A

SUMMARY OF INVENTION Technical Problem

Therefore, in order to solve the above problem, it is a first object ofthe present invention to provide a deforming element-included dispensingtip, a deforming element-included dispensing device, and a deformingelement-included dispensing processing method having a simple andcompact structure but still capable of handling several types of volumes(about several microliters to about several dozen milliliters) ofliquids with a high degree of precision and capable of performingefficient processing. It is a second object to provide a deformingelement-included dispensing tip, a deforming element-included dispensingdevice, and a deforming element-included dispensing processing methodnot requiring precision for watertightness, airtightness, and the likein production and quality control and capable of being provided at a lowcost, and in addition, reducing the burden in management, and having noopening other than an inlet unit, and capable of reliably preventingcross contamination. It is a third object to provide a deformingelement-included dispensing tip, a deforming element-included dispensingdevice, and a deforming-type dispensing processing method capable ofconsistently performing various kinds of complicated processing. It is afourth object to provide a deforming element-included dispensing tip, adeforming element-included dispensing device, and a deformingelement-included dispensing processing method capable of preventing theposition of the dispensing tip from deviating due to deforming and stillcapable of controlling the position with a high degree of precision byincluding a deformable portion in the dispensing tip formed by anon-deforming wall without forming an external wall of the dispensingtip with a deformable deforming wall. It is a fifth object to provide adeforming element-included dispensing tip, a deforming element-includeddispensing device, and a deforming element-included dispensingprocessing method capable of enabling the dispensing tip to beintegrated with a high degree of density and having many advantagesresulting from the integration by including a deformable portion in thedispensing tip formed by a non-deforming wall without forming anexternal wall of the dispensing tip with a deformable deforming wall. Itis a sixth object to provide a deforming element-included dispensingtip, a deforming element-included dispensing device, and a deformingelement-included dispensing processing method capable of reducing theload of quality control by including a deformable portion in thedispensing tip formed by a non-deforming wall without forming anexternal wall of the dispensing tip with a deformable deforming wall.Further, it is a seventh object to provide a deforming element-includeddispensing tip, a deforming element-included dispensing device, and adeforming element-included dispensing processing method capable ofefficiently, swiftly, and easily performing the processing such ashandling and measurement of a carrier by sealing a carrier bonded withor capable of being bonded with various kinds of substances such asbiological materials into a deformable container.

Solution to Problem

A first invention relates to a deforming element-included dispensing tipcomprising: a tip-shaped container formed with a non-deforming wallhaving an opening portion at an upper side and an inlet unit at a lowerside for allowing fluid to flow in and flow out; and a sealing plugattached to the opening portion so as to seal the opening portion,wherein the sealing plug is provided with a deforming element that has adeforming wall that is formed so as to be able to extend in a lowerdirection in the tip-shaped container in accordance with pressing froman outside and is formed so as to be urged to shrink or be able toshrink in an upper direction, and the deforming element is formed so asto be located inside the tip-shaped container.

In this case, “attachment” includes engagement, adhesion, thermaladhesion, ultrasonic adhesion, and welding. The sealing plug may be heldwith a hold-down plate and attached to an opening portion from above.Alternatively, it may be attached with an O ring interposedtherebetween. The “deforming wall” means a flexible wall that candeform. An elastic wall is also included within the range of flexiblewall. The “non-deforming wall” is a wall having such rigidity that thewall is neither deformed nor destroyed by an external force that candeform the deforming wall.

The deformation of the “deforming wall” is preferably deformation suchthat an internal volume is substantially determined in accordance withthe degree of applied deformation. More specifically, it is preferablethat the internal volume is uniformly determined by causing the insidesurrounded by the wall to be expanded or shrunk in accordance the degreeof pressing or pulling the deforming wall along any given deformingdirection or removing the force.

Examples of deforming walls include a wall formed with bellows, or awall including a spring and the like formed with an elastic memberexplained later or having an elastic force along a deforming direction.

In this case, the “bellows” means a planar member or a film memberformed with waves or folds having peaks and valleys formed along adirection crossing a predetermined deforming direction in asubstantially perpendicular direction, and that can bend at the peaksand valleys.

When the planar member or the film member formed with bellows is usedfor the wall surface enclosing in a tubular manner with the deformingdirection being the axis, the shape of the wave or fold may be made ofpeaks and valleys in a straight manner perpendicular to the deformingdirection, or a circumferential manner included in the planeperpendicular to the deforming direction, or in a closed curve manner (acurved line includes a straight line), or may be such that projectionsand depressions are formed to be inclined and formed in a spiral manner.

Examples of materials of the deforming element-included dispensing tipinclude resins such as polyethylene, polypropylene, polyester,polystyrene, polyvinyl, and acryl, and an elastic body such as rubber,and other flexible materials, or a combination thereof. The deformingelement-included dispensing tip is preferably transparent orsemi-transparent. Synthetic rubber, silicone, natural rubber, isoprenesynthetic rubber, and the like are used as the deforming wall. Forexample, polyethylene, polypropylene, polystyrene, and the like are usedas the non-deforming wall.

The size of the tip-shaped container of the deforming element dispensingtip is such that, for example, the length from the inlet unit to theopening portion or along the axis direction is several centimeters toseveral dozen centimeters, and the volume thereof is, for example, aboutseveral microliters to several dozen milliliters in accordance with thelength thereof.

In this case, the tip-shaped container is preferably formed such thatthe axis line passing the inlet unit and opening portion is formed alongthe vertical direction. The tip-shaped container is formed with, forexample, the resin, and as the deforming wall, for example, a sealingplug having the deforming element provided with bellows is formed withblow molding, and the tip-shaped container is formed with injectionmolding. Alternatively, all of them are formed with blow molding.

A second invention relates to a deforming element-included dispensingtip wherein the tip-shaped container comprises a deforming elementcontaining portion having the opening portion and capable of receivingthe deforming element so as to encompass a deformable range of thedeforming element, and a narrow tube portion formed to be narrower thanthe deforming element containing portion and having the inlet unit.

In this case, the length of the “deformable range” from the sealing plugin the vertical direction is configured to be equal to or longer thanthe maximum extension distance of the deforming element.

An accumulation portion is preferably provided to be in communicationwith the deforming element containing portion and the narrow tubeportion and capable of accumulating liquid sucked from the inlet unit,and gas is preferably stored in the deforming element containingportion, and sucking and discharging of the liquid is preferablycontrolled so that the liquid sucked to the narrow tube portion andaccumulation portion is accommodated therein. Therefore, the liquid doesnot contact with the deforming element, the liquid does not penetrateinto and remain in the space sandwiched between the deforming elementand the inner wall of the deforming element containing portion, and theliquid does not remain in the folds of the bellows of the deformingelement, so that a high degree of property in the constant amount can beensured.

Alternatively, without separately providing an accumulation portion,both of gas and liquid are allowed to be accommodated in the deformingelement containing portion, and in a state in which the deformingelement is not extended, in a minimum extension state, or in a shrunkstate, liquid may be accommodated up to a position where there is nocontact with the deforming element in the deforming element containingportion.

By forming the distal end of the narrow tube portion in a tapered shapeor a sharp shape, insertion into various containers is permitted, andthe sucking and discharging are simplified, and for a prepack typeaccommodation container of reagent and the like made by accommodating asolution including reagent, sample, or the like in advance and coveringthe opening portion thereof with a film, the film is stubbed by thenarrow tube portion, so that the solution accommodated in the containercan be sucked through the narrow tube portion.

A third invention relates to the deforming element-included dispensingtip, wherein the sealing plug has a depression surrounded by a tubularwall projecting to an inside of the tip-shaped container as thedeforming element, and the tubular wall comprises a bottom wall on whichforce is exerted from an outside to extend the deforming element, and aside wall having the deforming wall.

The tubular wall comprises the bottom wall and the side wall, and thebottom wall is formed so as to be able to be in contact with orconnected with a device for deforming the deforming element, and morespecifically, the bottom wall is formed so as to be able to be incontact with or connected with a pin which is a movable member explainedlater. At least a portion of the side wall is formed with the deformingwall. It is preferable to be accommodated in such a state that the sidewall of the deforming element and the inner wall of the deformingelement containing portion are in proximity to each other. Therefore,the deforming element can most greatly change the volume of thedeforming element containing portion.

A fourth invention relates to the deforming element-included dispensingtip, comprises a hold-down plate attached to the tip-shaped container atthe upper side of the sealing plug and holding the sealing plug from theupper side, and the hold-down plate is provided with an operation hole,and a protection wall formed so as to extend in the lower direction fromthe peripheral portion of the operation hole so as to be surrounded bythe deforming element.

The hold-down plate is formed with the non-deforming wall. The operationhole needs to be provided to allow contact or connection from theoutside to the deforming element through the hole. For example, amovable member comes into contact with or connects with the deformingelement. The protection wall is to prevent the deforming wall coveredwith the protection wall from being contacted from the outside, and forexample, the protection wall prevents contact between the deformingelement and the movable member inserted from the operation hole, andallows smooth operation by removing abrasion and resistance applied tothe movable member, and in addition, for the deforming element,attachment to the tip-shaped container is enforced, and abrasion andwear with the movable member are avoided, so that the degradation of thedeforming element can be delayed.

When the sealing plug has a depression, the protection wall extends inthe lower direction in the depression, and a portion of the tubular wallis covered with the protection wall.

A fifth invention relates to the deforming element-included dispensingtip, wherein the side wall comprises a flexible member, and is formedwith bellows.

A sixth invention relates to the deforming element-included dispensingtip, wherein the side wall has an elastic member.

A seventh invention relates to the deforming element-included dispensingtip, wherein the sealing plug has an elastic member, and is attached tothe opening portion of the tip-shaped container by using an O ring.

In this case, even if the sealing plug is attached to the tip-shapedcontainer without using adhesion nor welding, watertightness andairtightness can be maintained. Therefore, the sealing plug can bedetachably attached to the tip-shaped container.

An eighth invention relates to a deforming element-included dispensingtip in which a carrier bonded with or capable of being bonded with apredetermined substance is enclosed in the tip-shaped container in astate of capable of coming into contact with a fluid that flows in andout through the inlet unit.

In this case, the area where the carrier is enclosed is preferably “anarea where the inside can be measured from the outside”, and surroundedby the non-deforming wall having translucency, and in that area, thecarrier is preferably enclosed in such a state that it is not in contactwith the deforming element. The “enclosing” means that something that isaccommodated in the container having the inlet through which the fluidcan flow in and flow out (for example, carrier) is held so that it doesnot flow outside of the container through the inlet unit. Duringmeasurement, instead of allowing the carrier to freely move in thetip-shaped container, the carriers are preferably in a substantiallystationary state and movable from each other or with respect to anintroduced liquid. However, the carrier is not necessarily completelyfixed. In order to enclose the carrier, an enclosing portion may beprovided. The “enclosing portion” is a portion where the fluid can passthrough but the carrier cannot pass through in a case where the inletunit has such a size that allows the carrier to pass through. Theenclosing portion is made discretely from the non-deforming wall of thetip-shaped container or processing the non-deforming wall and isprovided so as to separate the tip-shaped container across the flowdirection of the fluid. The case where the enclosing portion isdiscretely provided includes a case where it is attached to thenon-deforming wall and a case where it is not attached thereto. The casewhere is made by processing includes a case where it is swaged. Shapesof the enclosing portion s include members provided so as to separate athin tube in a wheel shape, a cross shape, a straight line, a radialline, a mesh form, or a circular form, and a penetrating porous memberhaving penetration holes. The flow direction of the fluid may be in athin plate shape or a thin membrane manner. At least one enclosingportion is provided in order to prevent the carrier from flowing outfrom the inlet unit.

A solid object that can be bonded with a predetermined substance orcapable of being bonded with a predetermined substance is made of, forexample, resins holding a porous substance, resins holding apredetermined functional group or a predetermined chemical compound,organic substances including natural products such as fibroid substance,inorganic materials such as metal, semiconductor, glass, and silica.Examples of shapes of the carriers include a particle shape, a lineshape, a stick shape, a planer shape, a block shape, and the like. Itshould be noted that the “predetermined substance” includes biologicalchemical compounds such as genetic substances such as oligonucleotideand nucleic acid such as DNA and RNA, various kinds of chemicalcompounds such as proteins such as immunity substances, peptides, aminoacids, sugars, sugar chains, and the like, or living bodies themselvesor living tissues such as cells, bacteria, virus, and plasmid. The“predetermined substance” is not limited to a case where it is only onetype, and includes a case where there are multiple types of substances.The biological chemical compound is used to, e.g., detect bonding of,capture, separate or extract, a biological chemical compound serving asan acceptor having a bonding property with the biological chemicalcompound serving as a ligand. The acceptor corresponds to biologicalmaterials such as genetic substances such as nucleic acid, protein,sugar chain, peptide, and the like having bonding properties withgenetic substance such as the nucleic acid, sugar chain, peptide, andthe like. Instead of the biological chemical compounds, living bodiesthemselves such as cells, virus, plasmid, and the like can also be used.The carrier has a predetermined substance, e.g., a bonding body with aligand or an acceptor, or is fixed with a substance considered to have abonding property, for example, either an acceptor or a ligand.

The “bonding” means associating, with the carrier, at least one type ofpredetermined substance directly or via another type of substance.Examples of bonding include not only those based on covalent bonding andchemical adsorption but also those based on physical adsorption,hydrogen bonding, electrical interaction, and the like. A predeterminedchemical substance is fixed to the carrier by chemical adsorption orphysical adsorption, or is bonded by a special reaction with a bondingsubstance provided fixedly to the carrier, or other methods.Alternatively, when the carrier is formed with a porous member, anuneven member, and a fiber member, the reaction performance or thebonding performance with a biological material and the like may beenhanced.

Examples of materials of “carriers” include inorganic substances such asceramics, glass, silica, metal, semiconductor, semimetal, metal chemicalcompounds such as oxidized metal, and the like, and organic substancessuch as macromolecular substances such as rubber, latex, polystyrene,polypropylene, polyester, resin such as acryl, cellulose, fibersubstances such as nylon explained above, and natural substances such asnatural fibers such as silk. More specifically, for example, when afiber substance is used as an example, the carriers are silk and thelike, nylon (3-nylon, 6-nylon, 6,6-nylon, 6,10-nylon, 7-nylon, 12-nylonand the like) made of “polyamide-based polymers”, wholly aromaticpolyester such as PPTA (Poly-p-phenylene terephthalamide), heterocyclicring aromatic polymer, and the like. Alternatively, for example, fibrousbodies, porous bodies, and gel-like bodies may be used as the carriers.

For bonding, the carrier expresses or generates a functional group.Therefore, for example, peptide bonds of the “polyamide-based polymers”are hydrolyzed, so that the functional group used for the bonding of thebiological material is expressed or generated. Examples of functionalgroups that can be bonded with the biological materials include carboxylgroup-COOH, amino group-NH2, and inductions thereof. The diameters ofthe holes of the porous material suitable for bonding of the biologicalchemical compounds are, for example, equal to or less than severalmicrometers

The “carrier” is a solid of such a size that can be enclosed in thecarrier-enclosed deforming container and in which the position that isbonded or the position can be bonded with the predetermined substancecan be identified from the outside of the carrier-enclosed deformingcontainer. With the carrier, the position that is bonded or the positionthat can be bonded is associated with a predetermined position of acarrier with an interval therebetween so that the predeterminedsubstance is bonded or can be bonded, or in association with multiplepredetermined carriers, the carrier is preferably enclosed in thecarrier, so that, for example, the position that is bonded or theposition that can be bonded can be identified for example, with a onedimensional coordinate along the axis direction of the carrier-encloseddeforming container or in a random state. Examples of such carriersinclude one or more particle-like carriers, cubic carriers, line-likecarriers, stick-line carriers, strip-shaped carriers, flat plate-likecarriers, block-like carriers, and the like.

In this case, a solution including a predetermined substance labelledwith a labelling substance made of a light emitting substance such as afluorescence substance that may be bonded with the carrier itself or asubstance fixed to the carrier is brought into contact with the carrierin the tip-shaped container, so that the presence/absence of the bondingwith the biological material is measured by measuring the light emissionat each position, and therefore, the structure, the property, andpresence/absence of the object biological material can be analyzed.

The size of the deforming container is, e.g., a length between crossingpoints between the deforming wall surface and the inlet unit along theline passing through the inlet unit and surrounded by the accommodationunit, or the length in the axis direction is several centimeters toseveral dozen centimeters, and the volume thereof is about severalmicroliters to several dozen milliliters in accordance with the lengththereof.

It should be noted that the carrier may be a set of multipleparticle-like carriers or multiple particle-like carriers that arebonded with or that can be bonded with multiple types of chemicalsubstances and can be distinguished from the outside. In this case, the“particle-like carrier” is a particle-like solid having a size that canbe introduced and held in a portion of the tip-shaped container wherethe carrier is enclosed. Normally, a single particle-like carrier or aset of particle-like carriers correspond to a single type of multipletypes of chemical substances that are bonded or that can be bondedtherewith. The size of the particle-like carrier is such that, forexample, the diameter or the distance across is 0.1 mm to several mm. Inthe spatial portion where the particle-like carriers are enclosed, thevolume thereof is such that the spatial portion except the enclosedparticle-like carriers is a volume of, for example, several microlitersto several hundred microliters. A particle-like carrier or a set ofparticle-like carriers are labelled in accordance with the chemicalsubstance that is bonded or that can be bonded, and therefore, it is notnecessary to distinguish them in accordance with the arranged positionsof the enclosed particle-like carrier or the set thereof.

A ninth invention relates to a deforming element-included dispensing tipcartridge comprising a plurality of tip-shaped containers formed with anon-deforming wall so as to be integrally coupled and provided with aplurality of opening portions at an upper side and provided with aplurality of inlet units at a lower side for allowing fluid to flow inand flow out, and a plurality of sealing plugs attached to the openingportions so as to seal the opening portions, wherein the sealing plug isprovided with a deforming element that has a deforming wall that isformed so as to be able to extend in a lower direction in each of thetip-shaped containers in accordance with pressing from an outside andthat is formed so as to be urged to shrink or so as to be able to shrinkin an upper direction, and the deforming element is formed so as to belocated inside each of the tip-shaped containers.

In each deforming element-included dispensing tip, the tip-shapedcontainer is formed with the non-deforming wall, and the deformingelement is included in the tip-shaped container. Hence, multipledeforming element-included dispensing tips can be easily integrated intoa higher density by integrally forming a portion of the external wall ofthe tip-shaped container. In regard to the arrangement of the tip-shapedcontainers, they are arranged with a predetermined interval in a line ora planar manner (including a matrix form).

A tenth invention relates to the deforming element-included dispensingtip cartridge wherein each of the tip-shaped containers comprises adeforming element containing portion having the opening portion andcapable of receiving the deforming element so as to encompass adeformable range of the deforming element, and a narrow tube portionformed so as to be narrower than the deforming element containingportion and having the inlet unit.

In some cases the liquid sucked from the inlet unit according to thedeformation of the deforming element is sucked to the narrow tubeportion. In other cases, a portion of the liquid may be accommodatedinto the deforming element containing portion. In the latter cases, itis preferable that the deforming element and the deforming elementcontaining portion are formed so that the liquid does not come intocontact with the deforming element, or that such amount is controlled tobe preferably sucked. In this case, the magnetic field is given to thenarrow tube portion. When the accumulation portion is provided and is incommunication with the deforming element containing portion and thenarrow tube portion and is capable of accumulating the liquid suckedfrom the narrow tube portion, it is preferable that the deformingelement containing portions are integrally formed with each other. Butthe magnetic field can be given to the accumulation portion, and thenarrow tube portion can be inserted into each container, andaccordingly, the accumulation portions and narrow portions arepreferably provided with gaps, respectively.

An eleventh invention relates to the deforming element-includeddispensing tip cartridge, wherein the sealing plug has a depressionsurrounded by a tubular wall projecting to an inside of the tip-shapedcontainer as the deforming element, and the tubular wall comprises abottom wall on which force is exerted from an outside to extend thedeforming element, and a side wall having at least the deforming wall.

In this case, each of the sealing plugs may be attached to thetip-shaped container, or multiple sealing plugs which are adjacent toeach other and which are to be attached to multiple tip-shapedcontainers may be coupled with each other, and a line-like coupledsealing plug column may be formed.

A twelfth invention relates to the deforming element-included dispensingtip cartridge comprises a hold-down plate attached to the tip-shapedcontainers at the upper side of the sealing plugs and holding thesealing plugs from the upper side, and the hold-down plate is providedwith an operation hole in association with each of the sealing plugs,and a protection wall formed so as to extend in the lower direction fromthe peripheral portion of the operation hole and so as to be surroundedby the deforming element.

In this case, the hold-down plate is formed with the non-deforming wall,and may be attached to each tip-shaped container, or a coupled hold-downplate made by coupling multiple hold-down plates may be formed.

A thirteenth invention relates to the deforming element-includeddispensing tip cartridge, wherein the deforming element-includeddispensing tip cartridge is provided with two engagement units which area first engagement unit and a second engagement unit which are providedin a projecting manner or in a recessed manner with respect to anexternal direction at both ends along the arrangement direction thereof,and the first engagement unit is disposed at a first height, and thesecond engagement unit is disposed at a second height lower than thefirst height.

In this case, the first height and the second height are heightsmeasured from the inlet unit, and the first height is preferablyincluded within the height range of the deforming element containingportion.

The first engagement unit is used to provide support so as to cover theupper side of the deforming element-included dispensing tip cartridgelike the suspension unit of the dispensing head, and the secondengagement unit is used to give support to cover the lower side of thecartridge like the case of loading to the rack. Therefore, a transitionfrom one of the supports to the other of the supports can be performedsmoothly by just moving the cartridge using the dispensing head. Anexample of engagement unit is preferably, for example, a projectionportion or a depressed portion with respect to the external directionformed with the non-deforming wall and provided to be able to providesupport with not a single point but with approximately an externaldiameter from the deforming element containing portion to narrow tubeportion at the first or second height with respect to the thicknessdirection of the cartridge in order to ensure stability for support. The“arrangement direction” is a row direction or a column direction whenarranged in a matrix form.

A fourteenth invention relates to the deforming element-includeddispensing tip cartridge, wherein in a state of capable of coming intocontact with a fluid that flows in and out through the inlet unit, acarrier bonded with or capable of being bonded with a predeterminedsubstance is enclosed in an area which is inside of the tip-shapedcontainer and where the inside can be measured from the outside.

A fifteenth invention relates to a deforming element-included dispensingdevice comprising, one or more deforming element-included dispensingtips that has, a tip-shaped container formed with a non-deforming wallhaving an opening portion at an upper side and an inlet unit at a lowerside for allowing fluid to flow in and flow out, and a sealing plugattached to the opening portion so as to seal the opening portion,wherein the sealing plug is provided with a deforming element that has adeforming wall that is formed so as to be able to extend in a lowerdirection in the tip-shaped container in accordance with pressing froman outside and is formed so as to be urged to shrink or be able toshrink in an upper direction and that is provided so as to be positionedinside of the tip-shaped container, and a dispensing head configured tosuck and discharge liquid from and into the deforming element-includeddispensing tip by deforming the deforming element of the deformingelement-included dispensing tip.

In this case, the “sucking and discharging” means suction and/ordischarge. The reason why the deviation of the inlet unit of thedeforming element-included dispensing tip can be prevented by justattaching the tip-shaped container is because, in the deformingelement-included dispensing tip, the deforming element having thedeforming wall deforming during the sucking and discharging is includedin the tip-shaped container, and the deforming element is not related tothe external wall of the tip-shaped container, and therefore, when onlythe tip-shaped container is attached to the dispensing head, thedeviation of the inlet unit forming a part of the tip-shaped containercan be prevented. Therefore, this can be attached just like an ordinarycylinder-type dispensing tip.

A sixteenth invention relates to the deforming element-includeddispensing device further comprising a container group having aplurality of containers capable of accommodating various kinds ofsolutions and a head moving unit configured to move the dispensing headrelatively with respect to the container group, and wherein the inletunits can be inserted into the containers at a time.

In this case, when the inlet unit is disposed to face the lower side,then, the suction, the discharge, and the transition of the liquid canbe smoothly performed. The “solution” includes liquids including variouskinds of reagents, samples, chemical substances, or magnetic bodies. The“container” includes a container having multiple liquid accommodationunits and wherein each liquid accommodation unit is provided at theposition corresponding to the inlet unit.

A seventeenth invention relates to the deforming element-includeddispensing device, wherein the dispensing head comprises a tip supportportion capable of supporting the one or more deforming element-includeddispensing tips, and a movable member provided so as to be capable ofbeing in contact with or connected with the deforming element providedwith the sealing plug of the deforming element-included dispensing tip,and capable of performing forward/backward moving operation at a timealong a predetermined deforming direction of the deforming element bycoming into contact with or connected with the deforming element.

The movable member deforms the deforming element by performingforward/backward moving operation while it is in a state of being incontact with, contact with and detached from, or connected with thedeforming element. In order to support the deforming element-includeddispensing tip, support is provided to prevent the deviation and themovement of the tip-shaped container formed with only the non-deformingwall in the deforming element-included dispensing tip against the forceapplied by the movable member in two directions which are the extensiondirection and the shrinking direction in the inside thereof. In a caseof the deforming element-included dispensing tip, the deforming elementis included in the tip-shaped container, and the deforming elementdeforms in the vertical direction, and therefore, like a cylinder-typedispensing tip, it is sufficient to provide support so as to sandwich inthe vertical direction. It should be noted that the tip support portionof the dispensing head may include the tip arrangement holding unitcapable of arranging and detachably holding two or more deformingelement-included dispensing tips with a predetermined interval in a lineor a planar manner, or may include the deforming element-includeddispensing tip cartridge.

An eighteenth invention relates to the deforming element-includeddispensing device, wherein the deforming element-included dispensing tipcomprises a hold-down plate attached to the tip-shaped container at theupper side of the sealing plug and holding each of the sealing plugsfrom the upper side, and the hold-down plate is provided with anoperation hole in association with each of the sealing plugs, and aprotection wall formed so as to extend in the lower direction from theperipheral portion of the operation hole and so as to be surrounded bythe deforming element, wherein the movable member is provided to capableof be in contact with or connected with the deforming element via theoperation hole.

A nineteenth invention relates to the deforming element-includeddispensing device, wherein the dispensing head or the container groupcomprises a magnetic force unit capable of giving or removing a magneticfield into/from the inside of the tip-shaped container or thecontainers.

Therefore, for example, when a suspension in which many magnetic bodiesholding biological chemical compounds such as protein, peptide, aminoacid, DNA, RNA, oligonucleotide, and sugar chain are suspended is suckedfrom or discharged to the inside of the deforming element-includeddispensing tip or accumulated therein, the magnetic field is given tothe inside, so that the magnetic bodies are adsorbed to the inner wallof the tip, and the biological chemical compounds can be thereforeseparated.

A twentieth invention relates to the deforming element-includeddispensing device comprising a control unit configured to controldeforming of the deforming element and/or movement between thedispensing head and the container group on the basis of a number ofdeforming element-included dispensing tips or a structure thereof, aliquid which is to be sucked or discharged, a substance includedtherein, an amount thereof, an accommodation position thereof, atemperature or a concentration thereof, a processing content, or aninstruction.

The substance includes not only biological materials such as nucleicacid, protein, sugar chain, amino acid, and the like but also variouskinds of chemical substances including metal and the like. The “liquid”includes a solution and a suspension. The suspension includes, forexample, a suspension of magnetic bodies capable of being bonded withvarious kinds of substances due to reaction or bonded therewith due toreaction. The “processing” includes, for example, DNA extractionprocessing, immunity chemical inspection, analysis processing of variouskinds of biological materials, and the like.

A twenty first invention relates to the deforming element-includeddispensing device comprising a control unit configured to controldeforming of the deforming element on the basis of a change in terms ofthe position with respect to the deforming element, and a predeterminedchange of the deforming element based on a change in terms of theposition.

The “change in the position of the deforming element” is a change thatcan be applied to the deforming element from the outside of thedeforming element-included dispensing tip, and means a change in theposition coordinate at the contact point or the connection point that iscaused due to contact or connection of the movable member and the like.In a typical case, this means a one-dimensional change in the positionalong the deforming direction of the deforming element, and morespecifically, this means extension or shrink of the deforming element.The extension or shrink of the deforming element depends on the amountof movement of the movable member achieved by the motor in a case wherethis is done by moving the movable member reciprocally using the motor.

The “predetermined change of the deforming element” is a change otherthan the change in the position and includes one or more changesselected from, for example, a change in the volume of the deformingelement itself, a change in the size of area of a cross sectionperpendicular to the deforming direction of the deforming element, athickness of the deforming element itself, a change of the surface areaof the deforming element, or a change in the time of the deformingelement.

More specifically, the volume of the area surrounded by the inner wallof the tip-shaped container and the inner wall of the deforming elementis the area capable of accommodating the fluid, and the volume thereofcannot be correctly determined from the length in the axis direction ofthe deforming element due to the extension and shrink of the deformingelement on the assumption that the size of area of a cross sectionperpendicular to the axis direction of the deforming element isconstant. Therefore, a high accuracy of volume is obtained in view ofnot only the extension and shrink in the axis direction of the deformingelement but also a change of shrink, expansion, and the like in thecross section perpendicular to the axis direction caused thereby.However, these changes are changed because of complicated factors, andtherefore, it is difficult to uniquely determine the changes fromcalculation. Therefore, at multiple points, the relationship between theamount of the motor movement and the suction amount is measured, and theeach measurement point is complemented by an approximate expression. Asthe approximate expression for complementation, the optimum approximateexpression is chosen from a primary expression (broken line), apolynomial expression, a spline interpolation, and the like inaccordance with the required control precision and the shape of the tip.

The motor control of the suction and discharge amount is performed witha high precision in accordance with a conversion expression of thesuction amount and the motor control amount obtained in this manner.Further, in a case where there are hysteresis characteristics (in a casewhere there is a difference in the control amount between discharge andsuction), multiple conversion expressions, e.g., a conversion expressionfor suction and a conversion expression for discharge, are prepared, andare selectively used in accordance with the situation at that moment.

For example, when the deforming wall of the deforming element has anelastic member, the deforming of the deforming element is controlled inview of the change in the volume of the fluid accommodatable area of thetip-shaped container due to a change in the thickness of the deformingwall.

Further, in a case where there are hysteresis characteristics in thedeforming element as a change in time of the deforming element, themotor control amount differs between the suction and the discharge, andit is necessary to perform control using multiple conversionexpressions, e.g., a conversion expression for suction and a conversionexpression for discharge.

“Controlling based on something” means that control is performed bydetermining, for example, the change in the volume of the fluidaccommodatable area of the tip-shaped container, and more specifically,the change in the volume of the area capable of accommodating fluid (gasand liquid) in tip-shaped container which is the spatial area surroundedby the inner wall surface of the tip-shaped container and the inner wallsurface of the sealing plug (including the inner wall surface at thetip-shaped container inner side of the deforming element).

A twenty second invention relates to the deforming element-includeddispensing device, wherein a predetermined reference position is setwith regard to deforming of the deforming wall, and the deforming of thedeforming wall is controlled with reference to the reference position.

In this case, the “predetermined reference position” is determined bythe liquid amount treated in the processing, the volume that canaccommodate a fluid in the used deforming element-included dispensingtip, the content of the processing, the processing precision of thedeforming element-included dispensing tip, or the like.

For example, in a case where the liquid amount treated in the processingis a very small amount (for example, in a case of the order of severalmicroliters to several hundred microliters), or the volume of the useddeforming element-included dispensing tip is small, a case where theprocessing requires precision, or a case where the precision of theprocessing of the deforming element-included dispensing tip is not high,then, the reference position is adopted at the position along thedeforming direction of the movable member or the deforming element whenthe predetermined deforming is already applied to the deforming elementof the deforming element dispensing tip. Therefore, the control can beperformed with a high degree of precision. In this case, for example, itis preferable to configure setting so as to be able to discharge all thepredetermined maximum suction amount of the liquid into the deformingelement-included dispensing tip according to the predetermined maximumextension amount. Therefore, this can prevent the residual of the liquidin the deforming element-included dispensing tip because of thedischarge of the liquid from the deforming element-included dispensingtip

For example, the volume of the inside of the deforming element-includeddispensing tip defined in advance is denoted as V0, the distal endposition in the extension direction of the movable member or thedeforming element corresponding to the state is adopted as a reference,the maximum inside volume defined in advance according to the deformingof the deforming element-included dispensing tip is denoted as V1, andthe minimum inside volume defined in advance according to the deformingof the deforming element-included dispensing tip is denoted as V2(V1>V0>V2). In this case, it is preferable to set the reference positionso that the predetermined maximum suction amount V1−V0 of the liquidinto the deforming element-included dispensing tip satisfies suchrelationship that the predetermined maximum suction amount V1−V0 of theliquid into the deforming element-included dispensing tip is less thanthe predetermined maximum discharge amount V0−V2, and more specifically,V1−V0 is less than the predetermined maximum discharge amount V0−V2, andmore specifically, V1−V0<V0−V2 holds, and more specifically,(V1+V2)/2<V0 holds.

In this case, since this is the “predetermined maximum deformingamount”, it may not necessarily be the physically maximum deformingamount. On the contrary, when the maximum inside volume V1 and theminimum inside volume V2 are defined, it needs to be set in a range inwhich shrinking and urging are maintained in a case where the deformingelement uses a shrinkable elastic member made of rubber and the like.More specifically, this is because, when the extension of the deformingelement is configured to be large (V2 is configured to be smaller), theelastic member is stretched beyond the limit and may not be able to berestored back to the original shrink state.

Since “all the maximum suction amount can be discharged”, the “maximumdischarge amount” needs to have an amount equal to or more than the“maximum suction amount”. Therefore, the processing can be performedwithout worrying about the remaining amount of the liquid in thedeforming element-included dispensing tip.

On the other hand, when the amount of the treated liquid is large (forexample, in the case of the order of several milliliters) or in the casewhere the processing does not require so much precision, control can beperformed by referring to the position of the non-deforming state whichis not deformed in the deforming element-included dispensing tip. Insuch case, for example, this is a case where the position along thedeforming direction and in the state where the movable member has notcome into contact with the deforming element-included dispensing tip(for example, the position away from the tip by one millimeter) is takenas the reference position.

A twenty third invention relates to the deforming element-includeddispensing device, wherein the dispensing head or container groupcomprises a tip arrangement holding unit arranging two or more deformingelement-included dispensing tips with a predetermined interval in a lineor a planar manner and capable of detachably holding the two or moredeforming element-included dispensing tips, or a deformingelement-included dispensing tip cartridge connecting two or moredeforming element-included dispensing tips by arranging the two or moredeforming element-included dispensing tips with a predetermined intervalin a line or planar manner.

In this case, the “planar manner” is, for example, a matrix form, acircumference shape, multiple concentric circles, and the like.

The “matrix form” has an arrangement of two directions, i.e., a rowdirection and a column direction, and the directions do not need to benecessarily perpendicular to each other. The “predetermined interval”has an interval corresponding to the liquid accommodation unit of thecontainer provided in the container group. It is possible to preparethose having various kinds of pitches and numbers according to thenumber of treated solutions and the types and the amounts.

A twenty fourth invention relates to the deforming element-includeddispensing device, wherein the deforming element-included dispensing tipcartridge is provided with dispensing head suspension engagement unitsat both ends along the arrangement direction thereof, and the dispensinghead is provided with a frame body capable of surrounding one or moredeforming element-included dispensing tip cartridges so as to surround,from the upper side, a portion of the deforming element containingportion by an upper surface portion and both side surface portions, anda support portion capable of detachably supporting the deformingelement-included dispensing tip cartridge by engaging with thesuspension engagement unit at a lower side of the both side surfaceportion of the frame body, wherein in a case where the deformingelement-included dispensing tip cartridge is supported, the movablemember is provided to be capable of be in contact with or connected withthe deforming element of each of the deforming element-includeddispensing tips via the upper surface portion.

The deforming element-included dispensing tip cartridge is preferablyheld in the height range of the deforming element containing portionwhich may change according to the deforming operation. In this case, thefirst engagement unit corresponds to the dispensing head suspensionengagement unit.

The deforming element-included dispensing tip cartridge is preferablyarranged with not only the dispensing head suspension engagement unit ateach of both ends along the arrangement direction but also the rackloading engagement unit. In this case, the rack loading engagement unitcorresponds to the second engagement unit. Therefore, the dispensinghead suspension engagement unit is provided at the first height, and therack loading engagement unit is provided at the second height lower thanthe first height. The upper surface portion and both side surfaceportions may be plate-like walls, or may be formed with those in whichthe gap occupies almost all the area such as a mesh, a frame, and thelike.

A twenty fifth invention relates to the deforming element-includeddispensing device, wherein the tip arrangement holding unit comprises aplate provided with two or more penetrating holes provided with apredetermined interval in a line or a planar manner, and the deformingelement-included dispensing tips are inserted into the penetrating holesand held there, and the inlet unit of the deforming element-includeddispensing tip penetrates through the penetrating hole to be locatedbelow the plate, so that the sealing plug is held at an upper side ofthe plate.

A twenty sixth invention relates to the deforming element-includeddispensing device, wherein the deforming element-included dispensing tipcomprises an inner portion detection area, and the dispensing head isprovided with a light detection unit detecting a state of the insidethrough the inner portion detection area.

The “inner portion detection area” means an area for confirming ormeasuring the inside state. More specifically, this means an area for,e.g., confirming the sucking and discharging of the liquid (confirmationof presence/absence of the liquid), confirming the dispensing amount(confirmation of the liquid level), or measuring the carriers enclosedin the tip. Therefore, the area is preferably formed so as to easilyemit light into the inside and allow the light to penetrate through theinside. For example, it is formed to have a high degree of translucencywithout light diffuse reflection nor any optical distortion of the tip.

In this case, the “inner portion detection area” of the deformingelement-included dispensing tip is preferably provided in the narrowtube portion or the accumulation portion of the tip-shaped container.Therefore, when the inner portion detection area of the deformingelement-included dispensing tip is located below the plate, the lightdetection unit is also configured to be located below the plate.

When the carriers are enclosed, it is preferable to provide acarrier-enclosed deforming element-included dispensing tip comprising atip-shaped container formed with a non-deforming wall having an openingportion at an upper side and an inlet unit at a lower side for allowingfluid to flow in and flow out, and a sealing plug attached with theopening portion so as to seal the opening portion, and the sealing plugis provided with a deforming element having a deforming wall formed soas to be urged to shrink or be capable of shrinking in the upperdirection and capable of extending in the lower direction in thetip-shaped container in accordance with a pressing force from theoutside, and carrier bonded with or capable of being bonded with apredetermined substance enclosed in the tip-shaped container isprovided. Further, it is preferable to have the hold-down plate. It isalso possible to form the cartridge by coupling.

At this occasion, for example, the carrier is preferably enclosed in thenarrow tube portion or the accumulation portion of the tip-shapedcontainer. In this case, the “enclosing of the carrier in the narrowtube portion or the accumulation portion” means that the carrieraccommodated in the narrow tube portion or the accumulation portion isheld so as not to flow out of the narrow tube portion or theaccumulation portion via the inlet unit and the like.

It should be noted that there are various kinds of carriers, and theapplicant of the present application has already filedPCT/JP2002/001147, PCT/JP2004/001001, PCT/JP2005/007508 with regard tostring-like carriers, and has already filed PCT/JP2005/022775 (WO2006/062235 A1), PCT/JP2006/317337 (WO 2007/029616) with regard toparticle-like carriers, and has already filed PCT/JP2005/022776 (WO2006/062236 A1) with regard to planar carriers, and has already filedPCT/JP2006/300064 (WO 2006/073170) with regard to block-shaped carriers,and has already filed PCT/JP2007/061805 (WO 2007/145208) and the likewith regard to other carriers such as line-shaped, stick-shaped, flatplate-shaped, block-shaped, or particle-like carriers.

A twenty seventh invention relates to the deforming element-includeddispensing device, wherein the magnetic force unit provided with thedispensing head comprises two or more magnets provided to be able tocome close to and be departed from the tip-shaped containers of one ormore deforming element-included dispensing tips at a time.

For example, when the dispensing head comprises the tip support portion,and the tip support portion supports two or more deformingelement-included dispensing tips by attaching the tip arrangementholding unit arranging the two or more the deforming element-includeddispensing tips with a predetermined interval in a matrix form andcapable of detachably holding the two or more the deformingelement-included dispensing tips in such a manner that the deformingelement of each deforming element-included dispensing tip can bedeformed, the magnetic force unit comprises at least one comb-shapedmember or (the number of columns+1) comb-shaped members or (the numberof rows+1) comb-shaped members at most provided to be able to moverelatively in the row direction or the column direction of the deformingelement-included dispensing tips capable of being arranged in the matrixform and provided to have such a width that each can be inserted betweenthe columns or the rows in association with the predetermined intervaland extend in the row direction of the column direction, and a supportmember coupled with one end of the comb-shaped member, and each of thecomb-shaped members is provided with as many magnets as the number ofrows or the number of columns arranged with the predetermined intervalat the position corresponding to each of the deforming element-includeddispensing tips. When the magnetic field is given to the deformingelement-included dispensing tip, all the magnets may be moved so thatall the magnets come to the shortest distance to all the deformingelement-included dispensing tips, and when the magnetic field is removedor weakened, all the magnets may be completely retracted from the tiparrangement holding units arranged with the deforming element-includeddispensing tips, or may be moved so that each magnet is at theintermediate position of the predetermined interval of the deformingelement-included dispensing tips. It is sufficient to have only abouthalf the number of comb-shaped members as long as the magnets arrangedin a single comb-shaped member affect two tips arranged at both sidesthereof. It should be noted that the relative movement path of eachmagnet provided on the comb-shaped member with respect to the tip isalong a straight line or a curved line without crossing each tip.

A twenty eighth invention relates to the deforming element-includeddispensing device, wherein in a state of capable of coming into contactwith a fluid that flows in and out, a carrier bonded with or capable ofbeing bonded with a predetermined substance is enclosed in an area whichis inside of the tip-shaped container and where the inside can bemeasured from the outside.

A twenty ninth invention relates to a deforming element-includeddispensing processing method comprising a holding step of holding one ormore deforming element-included dispensing tips at a dispensing head,the deforming element-included dispensing tip comprises a tip-shapedcontainer formed with a non-deforming wall having an opening portion atan upper side and an inlet unit at a lower side for allowing fluid toflow in and flow out, and a sealing plug attached to the opening portionso as to seal the opening portion are provided, and in the sealing plug,a deforming element that has a deforming wall that is formed so as to beable to extend in a lower direction in the tip-shaped container inaccordance with pressing from an outside and that is formed so as to beurged to shrink or be able to shrink in an upper direction, and thedeforming element is formed so as to be located inside the tip-shapedcontainer, a movement step of moving the dispensing head, and adeforming step of inserting the inlet unit into a container in thecontainer group, and deforming the deforming wall surface at a time.

In this case, in the deforming step, it is preferably detected whetherprocessing is performed in accordance with instructions or not bydetecting the inside state of the deforming element-included dispensingtip or detecting absence/presence of liquid in the tip or the height ofthe liquid level.

A thirtieth invention relates to the deforming element-includeddispensing processing method, wherein in the holding step, a tiparrangement holding unit arranging two or more deformingelement-included dispensing tips with a predetermined interval in a lineor a planar manner and capable of detachably holding the two or moredeforming element-included dispensing tips or the deformingelement-included dispensing tip cartridge arranging and coupling two ormore deforming element-included dispensing tips in a line or a planarmanner with a predetermined interval is attached to a dispensing head sothat the deforming element-included dispensing tip can deform.

A thirty first invention relates to the deforming element-includeddispensing processing method, wherein in the deforming step, apredetermined reference position is set with regard to deforming of thedeforming wall surface, and the deforming of the deforming wall surfaceis controlled with reference to the reference position.

A thirty second invention relates to the deforming element-includeddispensing processing method, wherein the deforming step comprises astep of bringing the movable member to be in contact with or connectedwith the deforming element of the sealing plug, and a step of loweringthe movable member and/or raising the movable member.

A thirty third invention relates to the deforming element-includeddispensing processing method, wherein the deforming step comprises astep of providing an operation hole in association with each of thesealing plugs in a hold-down plate for holding each of the sealing plugsfrom the upper side and attached to the tip-shaped container at theupper side of the sealing plug and a protection wall formed so as toextend in the lower direction from the peripheral portion of theoperation hole and so as to be surrounded by the deforming element, andthe movable member is brought into contact with or connected with thedeforming element through the operation hole.

A thirty fourth invention relates to the deforming element-includeddispensing processing method comprising a step, in which a magnetic bodycapable of being bonded with a predetermined substance or bonded with apredetermined substance is suspended in the liquid, and the magneticbody is separated by causing the magnetic body to be adsorbed to theinner wall of the container or the accumulation portion by giving amagnetic field into an inside of a container of the accommodation unitor the container group.

A thirty fifth invention relates to the deforming element-includeddispensing processing method, wherein in the step of attaching thedeforming element-included dispensing tip cartridge to a dispensinghead, dispensing head suspension engagement units provided at both endsof the cartridge along an arrangement direction of the deformingelement-included dispensing tips are, by moving the dispensing head,engaged with support portions of a lower side of both side surfaceportions of a frame body provided on the dispensing head and having anupper surface portion and the both side surface portions, and thedeforming element-included dispensing tip cartridge is supported in sucha manner that the frame body surrounds the upper side of the deformingelement-included dispensing tip cartridge so as to include a part of thedeforming element containing portion thereof in the upper side, and inthe deforming step, the movable member is brought into contact with orconnected with the deforming element of each of the deformingelement-included dispensing tips through the upper surface portion.

A thirty sixth invention relates to the deforming element-includeddispensing processing method, wherein in a state of capable of cominginto contact with a fluid that flows in and out, a carrier bonded withor capable of being bonded with a predetermined substance is enclosed inan area which is inside of the tip-shaped container and where the insidecan be measured from the outside, and a detection step of detecting anoptical state in the tip-shaped container is further provided.

Advantageous Effects of Invention

According to the first invention, the ninth invention, the fifteenthinvention, or the twenty sixth invention, the deforming element includedinside of the tip-shaped container provided at the sealing plug of thetip-shaped container formed with the non-deforming wall is mechanicallydeformed, so that the liquid can be sucked and discharged.

Therefore, the deforming of the deforming element is guided along theinner wall of the tip-shaped container, so that the deforming element isprevented from deforming unintendedly, and highly reliable deforming canbe achieved. Therefore, it is not necessary to achieve deforming byseparately providing a holder for holding the tip-shaped container, likethe case where the deforming wall is provided outside of the tip-shapedcontainer.

Since the deforming element is included in the tip-shaped containerformed with the non-deforming wall even during the deforming, the entirelength in the axis direction can be shortened as compared with adeforming-type dispensing tip capable of accommodating the same amountof liquid. Then, the entire size of the device treating the deformingelement-included dispensing tip can be reduced

The dispensing processing can be achieved without using any complicatedfluid mechanical system such as piping for passing liquid or gasincluding a cylinder, and this reduces the size of the device andsimplifies the structure. Therefore, the device can be manufactured at alow cost and easily. In addition, a cylinder and the like having as muchvolume as a volume in the dispensing tip is not used, and therefore, inspite of the small size, a large quantity of liquid can be also treated.

The liquid processing such as suction, discharge, and the like isperformed by deforming the deforming element included in the tip-shapedcontainer, and therefore, there is no need to have engagement, sliding,and the like between members, which are required when a cylinder isused, and for this reason, a high degree of processing precision is notrequired, and the production is easy. In addition, completewatertightness and airtightness are obtained, and this reliably preventscross contamination, and therefore, highly reliable processing can beperformed.

The deforming element having the deforming wall is included inside ofthe tip-shaped container formed with the non-deforming wall, and theexternal force for deforming the deforming wall is directly applied tothe deforming element, and is not directly applied to the tip-shapedcontainer. Therefore, when an external force is applied to extend thedeforming element capable of extending in the lower direction, it issufficient to provide support so as not to move the tip-shaped containerin the vertical direction, and therefore, a simple support structure isused, and the deviation of the inlet unit is prevented, and therefore,highly reliable position control can be performed.

In the deforming element-included dispensing tip according to thepresent invention, the deforming element having the deforming wall isincluded in the tip-shaped container, and therefore, the amount of airaccommodated in the inside of the tip is limited to the amount of airaccommodated in a portion still smaller than the portion surrounded bythe inner wall of the tip-shaped container. On the other hand, in a caseof a cylinder-type dispensing tip used to connect with a cylinder via anozzle, the amount of air in not only the inside of the tip-shapedcontainer but also the inside of the nozzle is further added to theamount of air sucked into the cylinder, and when the deforming elementis provided to project out of the tip-shaped container, the amount ofair in not only the inside of the tip-shaped container but also theportion surrounded by the deforming element is added. Therefore, whenthe liquid is sucked and discharged using the tip-shaped container ofthe same volume, an air gap above the liquid level of the liquidaccommodated inside of the tip is small. Therefore, in the deformingelement-included dispensing tip and the like according to the presentinvention, the precision of the control of the sucking and dischargingcan be enhanced as a whole even in a case where there is a change in theshape and the thickness of the deforming element in the deforming of thedeforming element, the precision of the control of the sucking anddischarging can be enhanced as a whole.

The deforming element having the deforming wall is included inside ofthe tip-shaped container formed with the non-deforming wall, andtherefore, even if multiple deforming element-included dispensing tipsare disposed in close contact with each other, they are not in contactwith each other regardless of presence/absence of deforming of eachdeforming element included in each dispensing tip, and the deformingelement-included dispensing tips can be integrated with a high degree ofdensity.

When the deforming element-included dispensing tips are integrated,multiple deforming element-included dispensing tips can be deformedunder the same condition at a time, and therefore, by using thedeforming element-included dispensing tips, highly accurate positioncontrol and sucking and discharging control with a high degree ofreproducibility can be performed. In addition, multiple processing canbe performed in parallel using the deforming element-included dispensingtips, which is efficient, and even if many containers are arranged inclose contact with each other, highly reliable processing can beperformed.

Since the deforming element having the deformable deforming wall isincluded inside of the tip-shaped container formed with thenon-deforming wall, this prevents unnecessary external force from beingapplied to the deforming element except the deforming applied to thedeforming element in order to suck and discharge the fluid. Therefore,the deforming element is protected to prevent damages, destruction, ordeforming of the deforming element caused by unintended external force,or other unintended heating from the outside, change in the qualitycaused by chemical substances from the outside, and the management andthe handling of the deforming element-included dispensing tips can befacilitated

According to the second invention or the tenth invention, the deformingelement containing portion capable of accommodating the deformingelement is separately provided from the accumulation portion or thenarrow tube portion accumulating the liquid, so that this makes it easyto prevent the contact between the deforming element and the liquid andentry of the liquid into the deforming element containing portion, andthe liquid is prevented from remaining in the tip, and a high degree ofquantitative reliability in the sucking and discharging of the liquidcan be ensured. In addition, the cross contamination due to the liquidremaining in the tip can be prevented.

According to the third invention or the eleventh invention, in thesealing plug, the tubular wall formed with the side wall and the bottomwall having the deforming wall is provided so as to protrude inside ofthe tip-shaped container, and the depression is formed outside, so thatthe deforming guided by the inner wall of the tip-shaped container isperformed, and therefore, the range of the deforming is limited orrestricted in the tip-shaped container, and a highly reliable deformingcan be performed.

The external force is caused to be exerted on the bottom wall of thedepression provided in the sealing plug, and therefore, the force can beapplied in a stable state, and a highly reliable deforming can beperformed.

According to the fourth invention, the twelfth invention, the eighteenthinvention, or the thirty third invention, the sealing plug is held fromthe upper side, and the deforming element is prevented from projectingto the outside of the tip-shaped container, and in addition, when thedeforming element is deformed, abrasion of the deforming wall due tocontact of the movable member to the deforming wall and the degradationcaused by wear are prevented, and during the forward/backward movingoperation of the movable member unit, the resistance received from thedeforming wall due to contact with the deforming wall is removed oralleviated, and smooth deforming operation can be performed. Inaddition, by preventing unexpected deforming from being given to thedeforming element, highly reliable deforming control can be performed.

According to the fifth invention, in the deforming element, thedepression surrounded by the tubular wall projecting to the insidehaving the deforming wall forming the bellows on the side wall made ofthe flexible member, is formed, and is deforming with the bellows.Therefore, the size of the surface area and the thickness of thedeforming wall surface caused by the deforming are not changed, and thedeforming of the bellows is guided by the tip-shaped container, and thedeforming having a high degree of quantitative reliability can beperformed. In addition, since the deforming element is formed of a rigidmember, and therefore the deforming element is less likely to be broken.Further, the bending portion and the direction by the deformation aredetermined, and the regularity of the deforming and the quantitativereliability caused by the deforming are high.

According to the sixth invention, the deforming element is formed so asto have the deforming wall formed with the elastic member and have thedepression surrounded by the tubular wall projecting to the inside ofthe tip-shaped container. Therefore, even if the deforming element isextended, the deforming element can be easily shrink by removing theexternal force, and returned back to the original state, and thereforethe responsiveness is high.

According to the seventh invention, the sealing plug has the elasticmember, and is attached to the opening portion of the tip-shapedcontainer with the O ring interposed therebetween, and therefore,without being attached in a non-detachable manner by adhesion andwelding, the sealing plug can be detachably attached to the openingportion of the tip-shaped container while maintaining airtightness andwatertightness.

According to the ninth invention, in a case where multiple tip-shapedcontainers are integrally coupled so as to be partitioned from eachother and from the outside by using the non-deforming wall, thedeforming element having the deforming wall is included in thetip-shaped container, and therefore, each can be deformed without beingaffected by the coupling. Therefore, multiple deforming element-includeddispensing tips can be integrated with a high density.

According to the sixteenth invention, a required reagent and the likeare accommodated in the container in advance, and therefore, thedispensing processing can be automated easily.

According to the seventeenth invention or the twenty ninth invention,the movable member is brought into contact with or connected with thedeforming element, and can be moved along the deforming direction of thedeforming element, so that by using only the mechanical mechanismwithout contact with a processing target liquid, the processing such assuction, discharge, transition, and the like can be performed, and theportion that can come into contact with the liquid is limited to theinside of the tip-shaped container surrounded by the non-deforming wall,and therefore, the cross contamination can be reliably prevented.

Further, the movable member can be brought into contact with orconnected with the deforming element included inside of the tip-shapedcontainer, and the deforming element can be guided to the tip-shapedcontainer formed with the non-deforming wall, and therefore, thedeforming element can be deformed in a stable state, and highly reliableprocessing can be performed.

According to the nineteenth invention or the thirty fourth invention,the magnetic field is given to or removed from the inside of theaccommodation unit or the container, and therefore, the magnetic bodiesin the liquid in which the magnetic bodies are suspended are separatedby being adsorbed to the inside, and therefore, processing includingseparation processing can be automated throughout.

According to the twentieth invention, the deforming of the deformingelement and/or the movement of the dispensing head are controlled on thebasis of the structure and the like of the deforming element-includeddispensing tip, and therefore, the sucking and discharging can be donewith a high degree of precision in quantitative reliability.

According to the twenty first invention, when the control unit controlsthe deforming of the deforming element according to the change in theposition with respect to the deforming element, the movable member isbrought into contact or connected at the end of the deforming element toperform deforming in view of the change in the deforming element itself,and therefore, the sucking and discharging can be performed with a highdegree of precision of quantitative reliability regardless of the simplestructure.

According to the twenty second invention or the twenty eighth invention,the deforming is performed on the basis of the reference positioncapable of at least one of extension and shrinking of the deformingelement, and therefore, for example, when both of extension andshrinking of the deforming element are possible, the processing can beperformed efficiently and swiftly while immediately coping with both ofthem. By setting the reference position is a suitable manner, it ispossible to prevent the liquid from remaining in the deformingelement-included dispensing tip as a result of discharge of the liquid.

According to the twenty third invention or the thirtieth invention,multiple deforming element-included dispensing tips are arranged in thetip arrangement holding unit, or coupled deforming element-includeddispensing tip cartridges are adopted as a unit and provided in thedispensing head or the container group and configured to be movable, sothat the deforming element-included dispensing tips can be replacedswiftly, and the efficiency of the processing can be enhanced.

According to the twenty fourth invention or the thirty second invention,the dispensing head is moved by the head movement mechanism, so that thedeforming element-included dispensing tip cartridge can be detachablyattached to the frame body, and therefore, it is not necessary toprovide dedicated attachment mechanism, and the increase in the size ofthe device can be prevented. Depending on necessary, any number ofdeforming element-included dispensing tip cartridges can be attached,and therefore, efficiently control can be performed.

According to the twenty fifth invention, multiple penetrating holes areprovided through the plate as the tip arrangement holding unit, and thedeforming element-included dispensing tips are inserted into thepenetrating holes to be held therein, and therefore, the deformingelement-included dispensing tips can be arranged easily.

According to the twenty sixth invention, the state of the inside of thedeforming element-included dispensing tip is detected, whereby whetherthe suction and discharge are performed accurately according to aninstruction is confirmed by checking the presence/absence of the liquidand the water level of the liquid, and therefore, highly reliableprocessing can be performed.

According to the twenty seventh invention, magnets can be provided to beable to come close to and be departed from the tip-shaped containers ofthe deforming element-included dispensing tips at a time, and therefore,with a simple structure, the magnetic field can be easily applied toeach deforming element-included dispensing tip at a time.

According to the eighth invention, the fourteenth invention, the twentyeighth invention, or the thirty sixth invention, the effects explainedabove are achieved, and in addition, the carriers that are bonded withor that can be bonded with various kinds of substances such asbiological materials are enclosed in the tip-shaped carrier, and thedeforming elements are mechanically deformed, so that the liquid can besucked and discharged. Therefore, without using any complicated fluidmechanical mechanism such as piping and the like for passing liquid orgas such as a cylinder, suction of fluid into the tip-shaped container,contact between the fluid and the carrier, and the discharge areenabled, and by using a device that is easily operated, manually, orwith a simple structure, the device can be produced and the processingcan be performed at a low cost and easily.

While the carriers that are bonded with or that can be bonded with thepredetermined substance are enclosed in the tip-shaped container havingthe inlet unit, various kinds of processing, for example, reaction,cleaning, temperature control, separation, agitation, dispensing,clearness, isolation, elution, and extraction can be performed by justsucking and discharging the liquid and moving the carrier-encloseddeforming container, and therefore, the processing can be performedefficiently, swiftly, and easily.

Further, according to the present invention, the reaction with thepredetermined substance bonded with the carriers to the measurementthereof can be performed while still enclosed inside of the deformingelement-included dispensing tip of which opening is only the inlet unit,and therefore, throughout the object processing, the predeterminedsubstance is not contacted by another member or a person, and theprocessing can be performed, and therefore, while preventing crosscontamination, the processing can be performed reliably with a highdegree of reliability. In order to have a shape suitable for the liquidamount to be treated and the speed of the fluid, the carrier-encloseddeforming container is selected, so that various kinds of processing canbe coped with, and therefore, there is versatility and variations.

According to the present invention, the carriers are enclosed in thetip-shaped container and held therein, and therefore, this is not thecase where they are moved by applying fluid force, and treating of thecarriers and the measurement of the optical state can be facilitatedusing a simple control without performing complicated synchronizationcontrol and the like.

As explained above, the “area where the inside can be measured from theoutside” corresponds to the “inner portion detection area”.

BRIEF DESCRIPTION OF DRAWINGS

FIGS. 1A and 1B are top views and cross sectional views taken along lineA-A showing deforming element-included dispensing tips of a smallervolume according to a first embodiment of the present invention.

FIGS. 2A to 2D are top views and cross sectional views taken along lineA-A showing deforming element-included dispensing tips of variousvolumes according to the first embodiment of the present invention.

FIGS. 3A to 3D are explanatory diagrams illustrating operation of adeforming element-included dispensing tip according to the firstembodiment of the present invention.

FIG. 4 is a perspective view illustrating a deforming element-includeddispensing device according to the second embodiment of the presentinvention.

FIGS. 5A and 5B are a top view and a cross sectional view taken alongline A-A showing the deforming element-included dispensing device ofFIG. 4.

FIGS. 6A and 6B are partially enlarged view illustrating the deformingelement-included dispensing devices of FIG. 3 or FIG. 4 and aperspective view of a corresponding portion of a conventional technique.

FIGS. 7A and 7B are a top view and a cross sectional view taken alongline A-A of FIG. 5.

FIG. 8 is a perspective view illustrating eight deformingelement-included dispensing tip cartridge connecting eight deformingelement-included dispensing tips according to a third embodiment of thepresent invention.

FIG. 9 is an exploded perspective view illustrating the deformingelement-included dispensing tip cartridge of FIG. 8 when seen from theabove.

FIG. 10 is an exploded perspective view illustrating the deformingelement-included dispensing tip cartridge of FIG. 8 when seen from below

FIG. 11 is a cross sectional view illustrating the deformingelement-included dispensing tip cartridge of FIG. 8.

FIGS. 12A and 12B are cross sectional views illustrating the uppermostpoint and the lowermost point of movable members in the deformingelement-included dispensing tip cartridge of FIG. 8.

FIG. 13 is a perspective view illustrating the deformingelement-included dispensing device according to a fourth embodiment ofthe present invention when the deforming element-included dispensing tipcartridge of FIG. 8 is attached.

FIG. 14 is an enlarged perspective view illustrating a main portion of adispensing head of the deforming element-included dispensing deviceaccording to FIG. 13.

FIG. 15 is a back-side perspective view illustrating the deformingelement-included dispensing device according to FIG. 13.

FIG. 16 is a perspective view after the deforming element-includeddispensing tip cartridge according to FIG. 8 is attached to thedeforming element-included dispensing device according to FIG. 13 andsucking and discharging operation is performed by applying a magneticfield.

FIG. 17 is a perspective view illustrating a dispensing head is movedwhile a dripping prevention tray is pulled out after operation of FIG.13.

FIGS. 18A to 18D are cross sectional views illustrating a deformingelement-included dispensing tip into which a carrier is enclosedaccording to a fifth embodiment of the present invention.

FIGS. 19A to 19F are cross sectional views illustrating a deformingelement-included dispensing tip into which a carrier is enclosedaccording to another example of the fifth embodiment of the presentinvention.

FIGS. 20A and 20B are perspective views illustrating a light detectionunit and a magnetic force unit according to the fifth embodiment of thepresent invention.

FIGS. 21A and 21B are perspective views illustrating a light detectionunit according to the fifth embodiment of the present invention.

DESCRIPTION OF EMBODIMENTS

Subsequently, a deforming element-included dispensing tip according tothe first embodiment of the present invention and a deformingelement-included dispensing device according to the second embodimentusing the deforming element-included dispensing tip will be explainedwith reference to drawings.

FIGS. 1A and 1B are top views and cross sectional views taken along lineA-A illustrating deforming element-included dispensing tips 11, 11′ oftwo types of small capacities (for example, about 100 to 200microliters) according to the first embodiment of the present invention.

FIG. 1A illustrates an adhesion sealing-type deforming element-includeddispensing tip 11.

The deforming element-included dispensing tip 11 comprises a tip-shapedcontainer 15 formed with a non-deforming wall having an opening portion14 b at an upper side and an inlet unit 13 at a lower side for allowingfluid to flow in and flow out, and the deforming element-includeddispensing tip 11 comprises a sealing plug 19 adhered, using an adhesiveagent and the like, and attached to the opening portion 14 b so as toengage with and seal the opening portion 14 b, and the sealing plug 19is provided with a deforming element 12 that can extend in a lowerdirection in the tip-shaped container 15 in accordance with pressingfrom the outside in a lower direction along an axis line of thetip-shaped container and that has a deforming wall formed so as to beurged to shrink in the upper direction.

The tip-shaped container 15 comprises a deforming element containingportion 14 having the opening portion 14 b and capable of accommodatingthe deforming element 12 so as to encompass a deformable range of thedeforming element 12, a narrow tube portion 18 having a diameternarrower than the deforming element containing portion 14 and having theinlet unit 13 that can be inserted into various kinds of externalcontainers, an accumulation portion 16 capable of accumulating liquidsucked from the inlet unit 13 in communication with the deformingelement containing portion 14 and the narrow tube portion 18 and havinga diameter that is thicker than the narrow tube portion 18 but isthinner than the deforming element containing portion 14, and acone-shaped transition unit 17 disposed between the narrow tube portion18 and the accumulation portion 16. A flange 14 c is provided outside ofthe opening portion 14 b of the deforming element containing portion 14,and is used to support the deforming element-included dispensing tip 11and the deforming element. In this case, for example, when the volume is100 microliters, for example, the internal diameter of the deformingelement containing portion 14 is 6 mm, the internal diameter of theaccumulation portion 16 is 3 mm, and the internal diameter of the narrowtube portion 18 is 0.5 mm.

As the deforming element 12, the sealing plug 19 comprises a deformingwall formed with an elastic member such as rubber, and comprises atubular wall comprising a bottom wall 12 a and a depression 12 csurrounded by the side wall 12 b and projecting to the inside of thetip-shaped container 15. Reference numeral 14 a is a bottom inlet unitof the deforming element containing portion 14, and is formed in atapered manner to become narrower toward the accumulation portion 16.The sealing plug 19 may be attached with not only adhesion but alsothermal adhesion and ultrasonic adhesion. Since the sealing plug 19 isattached to the opening portion 14 b by adhesion, welding, and the like,the sealing plug 19 cannot be detached from the tip-shaped container 15.

FIG. 1B illustrates an O ring sealing-type deforming element-includeddispensing tip 11′.

Hereinafter, the same elements as the deforming element-includeddispensing tip 11 are denoted with the same reference numerals, andthose different therefrom are denoted with (′), so that they aredistinguished from each other.

The deforming element-included dispensing tip 11′ comprises a tip-shapedcontainer 15′ formed with a non-deforming wall having an opening portion14 b at an upper side and an inlet unit 13 at a lower side for allowingfluid to flow in and flow out, and a sealing plug 19′ detachablyattached to the opening portion 14 b to seal the opening portion 14 b bymaking use of the engagement between the O ring 19′a and the ring-shapedgroove 14′d, and the sealing plug 19′ is provided with the deformingelement 12.

The tip-shaped container 15′ comprises a deforming element containingportion 14′ comprising a ring-shaped groove 14′d engaging with the Oring 19′a in proximity to the opening portion 14 b and the openingportion 14 b and capable of accommodating the deforming element 12, anarrow tube portion 18 having a diameter narrower than the deformingelement containing portion 14′ and having the inlet unit 13 that can beinserted into various kinds of external containers, an accumulationportion 16 capable of accumulating liquid sucked from the inlet unit 13in communication with the deforming element containing portion 14′ andthe narrow tube portion 18 and having a diameter thicker than the narrowtube portion 18 but thinner than the deforming element containingportion 14′, and a funnel-shaped transition unit 17′ provided betweenthe narrow tube portion 18 and the accumulation portion 16.

Subsequently, FIGS. 2A and 2B illustrate deforming element-includeddispensing tips according to an embodiment of the present inventionhaving various sizes of and various types of deforming wall or sealingplug attachment methods.

FIG. 2A illustrates an adhesion sealing-type deforming element-includeddispensing tip 11 of a small volume explained in FIG. 1A for comparisonin terms of the size

FIG. 2B illustrates an adhesion sealing-type deforming element-includeddispensing tip 110 of a medium volume (for example, about 300microliters)

The deforming element-included dispensing tip 110 comprises a tip-shapedcontainer 150 formed with a non-deforming wall having an opening portion140 b at an upper side and an inlet unit 130 at a lower side forallowing fluid to flow in and flow out, and the deformingelement-included dispensing tip 110 comprises a sealing plug 190adhered, using an adhesive agent and the like, and attached to theopening portion 140 b so as to engage with and seal the opening portion140 b, and the sealing plug 190 is provided with a deforming element 120that can extend in a lower direction in the tip-shaped container 150 inaccordance with pressing from the outside in a lower direction along anaxis line of the tip-shaped container 150 and that has a deforming wallurged to shrink in the upper direction.

The tip-shaped container 150 comprises a deforming element containingportion 140 having the opening portion 140 b and capable ofaccommodating the deforming element 120 so as to encompass a deformablerange of the deforming element 120, a narrow tube portion 180 having adiameter narrower than the deforming element containing portion 140 andhaving the inlet unit 130 that can be inserted into various kinds ofexternal containers, an accumulation portion 160 capable of accumulatingliquid sucked from the inlet unit 130 in communication with thedeforming element containing portion 140 and the narrow tube portion 180and having a diameter that is thicker than the narrow tube portion 180but is thinner than the deforming element containing portion 140, and afunnel-shaped transition unit 170 disposed between the narrow tubeportion 180 and the accumulation portion 160. A flange 140 c is providedoutside of the opening portion 140 b of the deforming element containingportion 140, and is used to support the deforming element-includeddispensing tip 110.

As the deforming element 120, the sealing plug 190 comprises a deformingwall formed with an elastic member such as rubber, and comprises atubular wall projecting to the inside of the tip-shaped container 150and comprising a bottom wall 120 a and a depression 120 c surrounded bythe side wall 120 b. Reference numeral 140 a is a bottom inlet unit ofthe deforming element containing portion 140, and is formed in a taperedmanner to become narrower toward the accumulation portion 160. Thesealing plug 190 may be attached with not only adhesion but also thermaladhesion and ultrasonic adhesion. The sealing plug 190 cannot bedetached from the tip-shaped container 150

FIG. 2C illustrates an O ring sealing-type deforming element-includeddispensing tip 111 of a medium volume (for example, about 300microliters). The same elements as those of the deformingelement-included dispensing tip 110 of FIG. 2B are denoted with the samereference numerals, and explanation thereabout is omitted.

The deforming element-included dispensing tip 111 comprises a tip-shapedcontainer 151 formed with a non-deforming wall having an opening portion140 b at an upper side and an inlet unit 130 at a lower side forallowing fluid to flow in and flow out, and a sealing plug 191detachably attached to the opening portion 140 b to seal the openingportion 140 b by making use of the engagement between the O ring 191 aand the ring-shaped groove 141 c, and the sealing plug 191 is providedwith the deforming element 121.

The tip-shaped container 151 comprises a deforming element containingportion 141 comprising a ring-shaped groove 141 d engaging with the Oring 191 a in proximity to the opening portion 140 b and the openingportion 140 b and capable of accommodating the deforming element 121, anarrow tube portion 180 having a diameter narrower than the deformingelement containing portion 141 and having the inlet unit 130 that can beinserted into various kinds of external containers, an accumulationportion 160 capable of accumulating liquid sucked from the inlet unit130 in communication with the deforming element containing portion 141and the narrow tube portion 180 and having a diameter thicker than thenarrow tube portion 180 but thinner than the deforming elementcontaining portion 141, and the transition unit 170. A flange 140 c isprovided outside of the opening portion 140 b of the deforming elementcontaining portion 141, and is used to support the deformingelement-included dispensing tip 111.

As the deforming element 121, the sealing plug 191 comprises a deformingwall formed with a flexible member, and comprises a tubular wall in asubstantially circular tubular shape projecting to the inside of thetip-shaped container 151 and comprising a bottom wall 121 a and adepression 121 c surrounded by the side wall 121 b a part of which isformed with bellows. The bellows is a deforming wall disposed on aportion of the side wall 121 b of the deforming element 121 so as todivide the side wall 121 b to an upper side and a lower side andconfigured to deform in such a manner that the vertical direction is thedeforming direction. The bellows is in a screw shape, and as a wave formof a screw, crests (eight crests in this example) and roots (eight rootsin this example) are formed.

FIG. 2D illustrates an adhesion sealing-type deforming element-includeddispensing tip 112 of a large volume (for example, about 3 to 5milliliters). The deforming element-included dispensing tip 112comprises a tip-shaped container 152 formed with a non-deforming wallhaving an opening portion 142 b at an upper side and an inlet unit 132at a lower side for allowing fluid to flow in and flow out, and thedeforming element-included dispensing tip 112 comprises a sealing plug192 adhered, using an adhesive agent and the like, and attached to theopening portion 142 b so as to engage with and seal the opening portion142 b, and the sealing plug 192 is provided with a deforming element 122that can extend in a lower direction in the tip-shaped container 152 inaccordance with pressing from the outside in a lower direction along anaxis line of the tip-shaped container 152 and that has a deforming wallurged to shrink in the upper direction.

The tip-shaped container 152 comprises a deforming element containingportion 142 having the opening portion 142 b and capable ofaccommodating the deforming element 122 so as to encompass a deformablerange of the deforming element 122, a narrow tube portion 182 having adiameter narrower than the deforming element containing portion 142 andhaving the inlet unit 132 that can be inserted into various kinds ofexternal containers, and a funnel-shaped transition unit 172 disposedbetween the deforming element containing portion 142 and the narrow tubeportion 182 and the accumulation portion 162 and having a diameterthicker than the narrow tube portion 182 but narrower than the deformingelement containing portion 142. A flange 142 c is provided outside ofthe opening portion 142 b of the deforming element containing portion142, and is used to support the deforming element-included dispensingtip 112.

The sealing plug 192 comprises a deforming wall formed with a flexiblemember serving as the deforming element 122, and comprises a tubularwall projecting to the inside of the tip-shaped container 152 andcomprising a bottom wall 122 a and a depression 122 c surrounded by theside wall 122 b a part of which is formed with bellows. Referencenumeral 142 a is a bottom inlet unit of the deforming element containingportion 142, and is formed in a tapered manner to become narrower towardthe accumulation portion 162. The bellows is a deforming wall disposedon a portion of the side wall 122 b of the deforming element 122 so asto divide the side wall 122 b to an upper side and a lower side andconfigured to deform in such a manner that the vertical direction is thedeforming direction. The bellows is in a screw shape.

FIGS. 3A to 3D schematically illustrate the deforming element-includeddispensing tip 110 of the medium volume when it is supported by adispensing head 70 of a deforming element-included dispensing device 10explained later. This shows that a pin 20 of a movable member disposedon the dispensing head 70 is brought into contact with the bottom wall120 a of the deforming element 120 in the substantially circular tubularshape of the deforming element-included dispensing tip 110.

FIG. 3A illustrates a state in which the pin 20 is in contact with thebottom wall 120 a of the deforming element 120 but deformation is notapplied to the deforming element 120 (a state in which the lower end ofthe pin 20 is at level L1). More specifically, this indicates that thepin 20 of the movable member is moved in the upper direction from thedeforming element 120 of the deforming element-included dispensing tip110, the deforming element 120 is urged to shrink until this state isachieved. This indicates a state in which the fluid accommodatable areais a maximum volume (VL).

FIG. 3D illustrates a state in which the deforming element 120 is mostextended and the fluid accommodatable area is a minimum volume (VS), andthe lower end of the deforming element 120 is at a stop at the bottominlet unit 140 a of the deforming element containing portion 140.Therefore, this indicates a state in which no further extension ispossible (a state in which the position of the lower end of the pin 20is at level L4).

FIG. 3B is a maximum extension state in terms of control of thedeforming element 120, and the fluid accommodatable area is a minimumvolume V1 in terms of control (the position of the lower end of the pin20 is at level L3).

FIG. 3C is a minimum extension state in terms of control of thedeforming element 120, and the fluid accommodatable area is a maximumvolume V2 in terms of control (the position of the lower end of the pin20 at level L2). Then, in general, VL>V2>V1>VS holds. At this occasion,by defining a reference volume V0 of the fluid receivable area in termsof control as follows, all the amount of liquid sucked into thedeforming element-included dispensing tip 110 can be configured to bedischargeable.

More specifically, the maximum suction amount V2−V0 of the liquid suckedinto the dispensing tip determined in advance is preferably configuredsuch that the reference position satisfies a relationship less than themaximum discharge amount V0−V1 determined in advance, and morespecifically, the reference position satisfies V2−V0≤V0−V1, i.e.,(V1+V2)/2≤V0. The position of the lower end of the pin 20 corresponds tolevel L0 (L3<L0<L2). It should be noted that V1, V2 are in a range inwhich shrinkage urging of the deforming element formed with an elasticmember is maintained.

FIG. 4 illustrates a perspective view of the deforming element-includeddispensing device 10 according to the second embodiment using thedeforming element-included dispensing tip 11 according to the firstembodiment of the present invention.

The deforming element-included dispensing device 10 comprises adispensing head 70 in which 96 deforming element-included dispensingtips 11 of the small volume arranged in a matrix form of 12 rows×8columns is supported (96 elements are arranged in two directions, i.e.,12 rows in the column direction and 8 columns in the row direction) andwhich performs sucking and discharging of liquid from and to thedeforming element-included dispensing tip 11 by deforming the deformingwall of the deforming element 12 of each of the deformingelement-included dispensing tips 11, and 96 microplates 30 serving as acontainer group in which multiple wells 32 (96 wells in this case) thatcan accommodate various liquids, reagents, samples, and the like arearranged in a matrix form. It should be noted that the inlet units 13 ofthe deforming element-included dispensing tips 11 are arranged in such amanner that they can be inserted into the wells 32 at a time.

The dispensing head 70 comprises a tip support portion 24 supporting the96 small volume deforming element-included dispensing tips 11, and thetip support portion 24 comprises a tray 22 supporting the 96 deformingelement-included dispensing tips 11 and having 96 support holes 23penetrating therethrough having an internal diameter larger than theexternal diameter of the deforming element containing portions 14 of thedeforming element-included dispensing tips 11 arranged in the matrixform of 12 rows×8 columns but smaller than the external diameter of theflange 14 c, two tray grasping arms 27 grasping the tray 22 so as tosandwich the both sides of the tray 22 so that it can be engagedtherewith and detached therefrom, and a tip hold-down plate 28 havingpin holes 28 a arranged in a matrix form of 12 rows×8 columns and havinga size smaller than the external diameter of the opening portion 14 b ofthe deforming element-included dispensing tip 11 but in such a mannerthat the pin 20 is loosely inserted to reciprocally move in the verticaldirection, so that the 96 deforming element-included dispensing tips 11supported by the tray 22 is held from above. The tray 22 corresponds tothe tip arrangement holding unit.

The tray grasping arm 27 is attached to the support substrate 40 of thedispensing head 70 with a link 29 of the tray grasping arm drivingmechanism interposed therebetween in such a manner that the traygrasping arm 27 is slidably supported by the projection portions 27 aand in such a manner that the tray grasping arm 27 can be departedtherefrom. The tip hold-down plate 28 is attached by four tensionmembers 26 having springs urged to press in the lower direction withrespect to the support substrate 40.

The support substrate 40 of the dispensing head 70 is provided with amagnetic force unit 50. The magnetic force unit 50 includes multiplemagnets (96 magnets in this example) disposed to be able to, at a time,come close to and be departed from the accumulation portions 16 ofmultiple deforming element-included dispensing tips 11 (96 deformingelement-included dispensing tips 11 in this example).

The magnetic force unit 50 comprises six comb-shaped members 51 providedto be able to move in the row direction of the deformingelement-included dispensing tips 11 arranged with a predeterminedinterval in the matrix form (in a case of a matrix of 12 rows×8 columnsin FIG. 4) and provided to extend along the row direction and have sucha width that it can be inserted every other space between each row inassociation with the predetermined interval, and a support member 52coupled with one end of the comb-shaped member 51, and each of thecomb-shaped members 51 is such that as many magnets (511) as the numberof columns (eight magnets (511) in this example) arranged with thepredetermined interval at positions corresponding to the accumulationportions 16 of the deforming element-included dispensing tips 11 areprovided on both side surfaces of the comb-shaped member 51. When themagnetic field is applied to, all the magnets are moved to a position ofthe shortest distance to all of the deforming element-includeddispensing tips 11, and when the magnetic field is eliminated, all themagnets are completely retracted from the tip support portion 24

For the support substrate 40, a linear step motor 54 for reciprocallydriving the comb-shaped member 51 is provided, and the comb-shapedmember 51 is moved in the row direction by reciprocally moving thedriving plate 56 coupled via a driving shaft 55, the comb-shaped member51 and guide rods 53.

On the upper side of the support substrate 40, a movable member drivinglinear step motor 60 is provided to move the 96 pins 20 which aremovable members in the vertical direction, so that the 96 pins 20coupled via a driving shaft 61, a driving plate 63, and guide rods 62 ofthe motor 60 are moved in the vertical direction.

The support substrate 40 is provided with the vertical directionmovement mechanism of the dispensing head, i.e., guide members 42engaging with guide rails 41 disposed on a side plate 46 of a devicefixed to a stage on which the microplate 30 is mounted, so that thedispensing head 70 provided on the side plate 46 can be moved in thevertical direction by the linear step motor 44 driving in the verticaldirection.

FIG. 5A is a top view illustrating the deforming element-includeddispensing device 10. FIG. 5B is a cross sectional view taken along lineA-A of FIG. 5A.

Reference numeral 29 a denotes a step motor for driving a tray graspingarm, and by rotating a predetermined angle, the tray 22 can be graspedand released

The 96 pins 20 are arranged in a matrix form of 12 rows×8 columnsextending in the lower direction from the lower side of the plate-shapedmovable member 21 coupled with the driving shaft 61 of the motor 60.

Subsequently, in a case where the deforming element-included dispensingdevice 10 performs various kinds of processing, for example, extractionprocessing of DNA, RNA, on 96 samples at a time will be explained.Multiple microplates 30 accommodating, in advance, 96 samples, amagnetic particle suspension covered with silica, and the like, nucleicacid extraction reagent solution, cleaning solution, eluate, and thelike are arranged and prepared on the stage in the order of processing.Processing is performed on each of the multiple microplates 30 using,for example, a commonly used XY axis moving mechanism, not shown, suchas a ball screw and a step motor while the deforming element-includeddispensing device 10 hung from the upper side of the microplates 30 isrelatively moved in order.

Now, a case where cleaning is going to be performed upon an alreadycompleted step of causing magnetic particles to bond DNA of an objectfrom a sample will be explained. The dispensing device 10 is positioned,for example, above the microplate 30 accommodating cleaning solution ineach well 32 and the deforming element-included dispensing tips 11 arepositioned immediately above each well 32. At this occasion, magneticparticles bonded with DNA of an object in the processing of the previousstep are adsorbed to the inner wall of the accumulation portion 16 ofeach deforming element-included dispensing tip 11 and are in a condensedstate in a pellet form.

More specifically, at this occasion, six comb-shaped members 51 providedwith 96 magnets provided on the dispensing head 70 of the dispensingdevice 10 extends along the row direction between six rows of the 96deforming element-included dispensing tips 11 arranged in a matrix form,and are in proximity to the accumulation portions 16 of the deformingelement-included dispensing tips 11.

Therefore, by driving the movable member driving linear step motor 60,the pins 20 provided so as to project in the lower direction of themovable member 21 are caused to be located in the lower direction to areference position defined in advance, so that the deforming elements 12of the deforming element-included dispensing tips 11 are extended in thelower direction to a state defined in advance.

Subsequently, the dispensing head 70 is descended by driving the linearstep motor 44, and the inlet unit 13 of each deforming element-includeddispensing tip 11 is inserted into each well 32 of the microplate 30.

Subsequently, the comb-shaped member 51 of the magnetic force unit 50 isretracted from between the rows of the deforming element-includeddispensing tips 11 by the linear step motor 54, so that the magneticfields in the accumulation portions 16 are eliminated.

Subsequently, the pins 20 are moved in the upper direction by drivingthe movable member driving linear step motor 60, and the pins 20 aremoved to the upper limit position in terms of control defined in advancecorresponding to level L2 shown in FIG. 3C, so that the cleaningsolution in the well 32 is sucked at a time to be introduced to theaccumulation portion 16 of each deforming element-included dispensingtip 11, and it is brought into contact with the magnetic particles stillcondensed on the inner wall of the accumulation portion 16 in such astate that the magnetic field is removed.

Subsequently, the pins 20 are moved in the lower direction with respectto the cleaning solution and the magnetic particles introduced to theaccumulation portion 16 by moving the movable member driving linear stepmotor 60, so that the pins 20 are moved to the lower limit positiondefined in advance beyond the reference position corresponding to levelL3 as shown in FIG. 3B, and therefore, the entire amount of cleaningsolution in the accumulation portion 16 and the magnetic particles aredischarged through the inlet unit 13 into the 96 the wells 32 at a time.

In this manner, the sucking and discharging are repeated until thecondensation of the magnetic particles on the inner wall of theaccumulation portion 16 is solved, and the magnetic particles areresuspended in the cleaning solution, and the cleaning solution and theobject substance of the magnetic particles are sufficiently brought intocontact and processed.

When the reaction and resuspension of the cleaning solution and theobject substance are finished as described above, the comb-shaped member51 of the magnetic force unit 50 is moved into between the rows again,and the magnetic field is given to the inside of the accumulationportion 16 of each deforming element-included dispensing tip 11. In thisstate, the pins 20 are moved in the upper direction to the upper limitposition in terms of control by driving the movable member drivinglinear step motor 60, and the resuspended magnetic particle suspensionis sucked and introduced to the accumulation portion 16, so that themagnetic particles are adsorbed to the inner wall by the magnetic fieldagain.

Subsequently, the pins 20 are moved to the lower limit position in termsof control, so that all the residual liquid other than the magneticparticles adsorbed to the inner wall is discharged to each well 32 at atime, and then, the processing in this step is finished.

Then, the dispensing device 10 is moved to a microplate in a subsequentstep, and subsequent processing is performed.

FIGS. 6A and 7A illustrate only a portion of the tip support portion 24,the movable members 21, and the pins 20 in a case where the sucking anddischarging processing is performed using the 96 deformingelement-included dispensing tips 11 according to the present invention.

On the other hand, FIG. 6B and FIG. 7B illustrate a cylinder 231 and aplunger 220 in a case where sucking and discharging processing isperformed using 96 dispensing tips (tip-shaped containers) 15 used byattaching the opening portions thereof to 96 nozzles 230 according to aconventional example. For comparison, in this case, the drawings areshown using the same tray 22 of tip arrangement holding unit as that ofthe present invention and the tip-shaped container 15 used for thedeforming element-included dispensing tip 11 according to the presentinvention.

Then, it is understood from the sizes in the drawings that how thepresent invention reduces the device size and simplifies the devicestructure.

Further, in the device according to the embodiment of the presentinvention, it is not necessary to attach the dispensing tips to thenozzles by engaging the dispensing tips with the nozzles, and therefore,it is not necessary to have a force as much as about 100 kg for causingmany dispensing tips, for example, 96 dispensing tips, to be engagedwith the nozzles at a time, and therefore, the device according to theembodiment of the present invention is suitable for integration.

Therefore, the dispensing tip does not need a high degree of rigidity toavoid the damage of the dispensing tip due to the force applied when itis attached, or the lifetime of the tip is extended, and the burden ofquality control can be simplified.

Further, the deforming element is included, and the external wall of thedispensing tip is formed with the non-deforming wall, and therefore, thehigher degree of density in the integration can be achieved, andfurther, the integration can be achieved in an integrated manner.

Instead of moving the plunger to slide on the inner wall of thecylinder, the sealing deforming element is extended and shrunk by themovable member, and therefore, watertightness and airtightness are high,and in addition, the resistance is low, and therefore, the driving canbe done without adding a very large force.

The deforming element is located in the inside of the tip-shapedcontainer formed with the non-deforming wall, and therefore, thedeformation of the deforming element is restrained, and the deformationcan be done with a high degree of consistency.

Subsequently, FIG. 8 to FIGS. 12A and 12B illustrate a deformingelement-included dispensing tip cartridge 115 according to a thirdembodiment of the present invention. In the deforming element-includeddispensing tip cartridge 115, eight deforming element-includeddispensing tips 113 arranged in a single line are integrally connected.

As shown in FIGS. 8 and 9, each deforming element-included dispensingtip 113 comprises a tip-shaped container 153 formed with a non-deformingwall having an opening portion 143 b at an upper side and an inlet unit133 at a lower side for allowing fluid to flow in and flow out, asealing plug 193 adhered, using an adhesive agent and the like, andattached to the opening portion 143 b so as to engage with and seal theopening portion 143 b, and a hold-down plate 173 attached to thetip-shaped container 153 at the upper side of the sealing plug 193 andholding the sealing plug 193 from the upper side.

As shown in FIG. 8 to FIGS. 12A and 12B, the tip-shaped container 153comprises a deforming element containing portion 143 having the openingportion 143 b and capable of accommodating the deforming element 123 soas to encompass a deformable range of the deforming element 123, anarrow tube portion 183 in communication with the deforming elementcontaining portion 143 and having a diameter narrower than the deformingelement containing portion 143 and having the inlet unit 133 that can beinserted into various kinds of external containers, and a transitionunit 143 a disposed between the narrow tube portion 183 and thedeforming element containing portion 143. A flange 143 c is providedoutside of the opening portion 143 b of the deforming element containingportion 143. For example, when the volume of each deformingelement-included dispensing tip 113 is 250 microliters (which is in arange of medium volume), for example, the entire length in the axisdirection is 75 mm, and the internal diameter of the deforming elementcontaining portion 143 is 6 mm, and the internal diameter of the narrowtube portion is 0.85 mm.

These eight tip-shaped containers 153 are formed in a single line as awhole by connecting the deforming element containing portions 143adjacent to each other with a non-deforming wall connection plate 115 d.A rack loading projection portion 115 a and a suspension projectionportion 115 b explained later further extending in the row direction andrespectively engraved in two parallel non-deforming wall vertical platesdisposed with a distance approximately equivalent to the externaldiameter of the deforming element containing portion 143 in thethickness direction of the cartridge 115 are respectively provided atboth ends of the connection plate 115 d. At the upper ends of thetip-shaped containers 153, eight tip-shaped containers 153 are connectedin a single line by the container connection horizontal plate 115 cprovided with opening portions 143 b. The tip-shaped containerconnection horizontal plate 115 c is provided with multiple hold-downplate fixing holes (18 hold-down plate fixing holes 173 d in thisexample) for attaching a hold-down plate 173 explained later.

The sealing plug 193 comprises a deforming wall formed with an elasticmember such as rubber as the deforming element 123, and comprises atubular wall projecting to the inside of the tip-shaped container 153and comprising a depressions 123 c surrounded by a bottom wall 123 a anda side wall 123 b. It should be noted that the transition unit 143 a isformed in a tapered manner to become narrower toward the narrow tubeportion 183 at the bottom inlet unit of the deforming element containingportion 143. Since the sealing plug 193 is attached to the openingportion 143 b by adhesion, welding, and the like, the sealing plug 193cannot be detached from the tip-shaped container 153. These eightsealing plugs 193 are connected with each other to form a sealing plugcolumn 115 e in a single line.

As shown in FIG. 8 to FIGS. 12A and 12B, the hold-down plate 173 isattached to the tip-shaped container 153 at the upper side of thesealing plug 193, and the hold-down plate 173 is provided with anoperation hole 173 a corresponding to each sealing plug 193, and atubular protection wall 173 b formed so as to extend in the lowerdirection from the peripheral portion of the operation hole 173 a. Theeight hold-down plates 173 are coupled by a non-deforming wall to form ahold-down plate column 115 f.

The hold-down plate column 115 f is provided with a fixing claw 173 cfor attaching the hold-down plate column 115 f to the tip-shapedcontainer connection horizontal plate 115 c.

FIGS. 12A and 12B illustrate a used state where pins 200 serving asmovable members explained later are inserted into deforming elements 123of the deforming element-included dispensing tips 113 of the deformingelement-included dispensing tip cartridge 115. For example, in FIG. 12A,the pin 200 serving as the movable member is at the uppermost positionin use, and reference numeral 1 denotes a liquid level in the maximumsuction state. FIG. 12B is the lowermost position when the pin 200serving as the movable member is in use, and in this state, the liquidis completely discharged from each deforming element-included dispensingtip 113. A predetermined reference position is preferably anintermediate point of them both.

FIG. 13 illustrates a deforming element-included dispensing device 100according to a fourth embodiment of the present invention. However, 96deforming element-included dispensing tips 113 in which the eightdeforming element-included dispensing tip cartridges 115 according tothe third embodiment are arranged in 12 rows (columns) are in a state ofbeing placed on the rack 220, and are not yet attached to the deformingelement-included dispensing device 100. At both ends of the eightdeforming element-included dispensing tip cartridge 115 in thearrangement direction (Y axis direction in the drawing) of the deformingelement-included dispensing tips 113, rack loading projection portions115 a serving as second engagement units provided to protrude in theouter direction are engaged with depressed portions 221 formed on therack 220 and the eight deforming element-included dispensing tipcartridge 115 is loaded on the rack 220. It should be noted that asuspension projection portion 115 b serving as a first engagement unitprovided at a first height position higher than the second heightposition of the second engagement unit is in a state capable of engagingwith a support edge portion 273 of the frame body 270.

As shown in FIG. 13, the deforming element-included dispensing device100 comprises a deforming element-included dispensing tip rack 220accommodating the 12 eight deforming element-included dispensing tipcartridges 115 where the 96 deforming element-included dispensing tips113 are arranged in a matrix form of 12 rows×8 columns (96 elements arearranged in parallel in two directions, i.e., 12 rows in the columndirection and 8 columns in the row direction), a dispensing head 71capable of supporting, at a time, 12 rows of the eight deformingelement-included dispensing tip cartridges 115 accommodated in thedeforming element-included dispensing tip rack 220 and sucking anddischarging the liquid from the deforming element-included dispensingtips 113 or to the deforming element-included dispensing tips 113 bydeforming the deforming wall of the deforming element 12 of eachdeforming element-included dispensing tip 113, the 96 microplates 30serving as the container group which can accommodate various kinds ofliquids, reagents, samples, and the like and in which multiple wells 32(96 wells 32 in this example) are arranged in a matrix form, and an Xaxis moving mechanism 47 and a Z axis moving mechanism 48 serving as ahead moving unit capable of respectively moving the dispensing head 700with respect to the 96 microplates 30 serving as the container group inthe X axis direction and the Z axis direction.

The X axis moving mechanism 47 comprises an X axis driving belt-likeplate 475 extending in the X axis direction, two rails 474, i.e., upperand lower rails 474, disposed in parallel at the upper and lower sidesof the front side along the X axis direction on the X axis drivingbelt-like plate 475, and four sliding unit 476 provided along the rails474 in a slidable manner and engaging with the timing belt 473 to beable to move in the X axis direction with the timing belt 473, and amotor 471 for rotating and driving the timing belt 473 is provided atthe back side of the X axis driving belt-like plate 475.

The four sliding units 476 are attached to the X axis moving body 477,and with the movement of the sliding unit 476, the X axis moving body477 can move along the X axis. The X axis moving body 477 comprises theZ axis moving mechanism 48 for moving the dispensing head 71 along the Zaxis, a dripping prevention mechanism 80 for preventing liquid fromdropping from the deforming element-included dispensing tip 113, and themagnetic force unit 500 for giving magnetic force into the inside of thedeforming element-included dispensing tip 113.

The Z axis moving mechanism 48 comprises a Z axis driving motor 481attached to an upper plate 49 of the X axis moving body 477, a rotor 482driven to rotate and driven by the Z axis driving motor 481, and a rotor483 driven to rotate by the rotor 482 via the timing belt 484. The rotor483 is coupled with a ball screw 485 extending in the lower direction,and with the rotation of the rotor 483, the ball screw 485 rotates. Theball screw 485 is screwed with an upper side substrate 74 constitutingthe dispensing head 71, and with the rotation and driving of the Z axisdriving motor 481, the upper side substrate 74 constituting thedispensing head 71 can move along the guidance pillar 486 in thevertical direction. Likewise, in synchronization with the upper sidesubstrate 74, the substrate 75 and a tip suspension unit are also drivenin the vertical direction.

The upper side substrate 74 has a rotor 76 attached to a pin drivingmotor and is driven to rotate via a rotor 72 and a timing belt 73 drivento rotate by the pin driving motor, and the rotor 76 is coupled with aball screw 66. The ball screw 66 is screwed with a pin driving upperplate 64, and the pin driving upper plate 64 is coupled with a pinarrangement plate 201 arranged with the 96 pins 200 arranged in thematrix form in such a manner that four connection pillars 65 penetratethrough the substrate 75 of the dispensing head 71. When the pin drivingupper plate 64 moves upward and downward according to the rotation ofthe pin driving motor, the pin arrangement plate 201 arranged with the96 pins 200 moves upward and downward by means of the four connectionpillars 65. Then, the pins 200 are inserted into pin holes 274 providedin the frame body 270 of the suspension unit attached to the substrate75 of the dispensing head 71, and the deforming element of eachdeforming element-included dispensing tip 113 provided in associationwith the pin hole 274 can be deformed.

FIG. 14 enlarges and illustrates the main portion of the dispensing head71. The suspension unit is attached to the substrate 75 of thedispensing head 71. The suspension unit comprises a frame body 270capable of enclosing multiple deforming element-included dispensing tipcartridges 115 (12 deforming element-included dispensing tip cartridges115 in this example) coupled with multiple deforming element-includeddispensing tips 113 (eight deforming element-included dispensing tips113 in this example) which are surrounded by three walls, i.e., an upperwall 272 corresponding to the upper surface portion and both side walls271 corresponding to the both side surface portions, support edgeportions 273 provided to be able to hold the suspension projectionportions 115 b serving as the first engagement unit provided at bothends disposed to protrude in the external direction along the rowdirection (longitudinal direction, Y axis direction) of the deformingelement-included dispensing tip cartridge 115 so as to protrude in theinner side direction at the lower side of the both side walls 271 of theframe body 270, and pin holes 274 made through the upper wall 272 sothat the pins 200 can be inserted into the positions corresponding tothe deforming element-included dispensing tips 113, and the distancebetween the both side walls and the height and the depth of the bothside walls are defined so that the multiple deforming element-includeddispensing tip cartridges can be suspended in such a state that they arearranged in a matrix form.

Each support edge portion 273 is arranged with a fixed projectionportion 275 or a depressed portion of the cartridge 115 having a lengthcorresponding to an interval between a pair of suspension projectionportions 115 b engraved in the two parallel vertical plates provided foreach cartridge 115 with an interval corresponding to the thickness ofthe deforming element-included dispensing tip cartridge 115(approximately the external diameter of the deforming element containingportion in this example). Therefore, the cartridge 115 is supported bythe frame body 270 provided with the suspension unit and can preventdeviation during deforming operation.

FIG. 14 further illustrates the dripping prevention mechanism 80. Thedripping prevention mechanism 80 is provided on the X axis moving body477, and does not move in the Z axis direction like the dispensing head71. The dripping prevention mechanism 80 is provided to reciprocallymove in the Y axis direction, and comprises a dripping prevention tray81 capable of receiving droplets from each deforming element-includeddispensing tip 113 suspended in such a manner that the tray 81 advancesto the lower side of the frame body 270 provided with the suspensionunit, and the tray 81 is coupled with a timing belt 82 stretched betweena rotor 85 (see FIG. 15) driven to rotate by the driving motor 84 and arotor 83, and moves according to the movement of the timing belt.

FIG. 15 illustrates a deforming element-included dispensing device 100according to the fourth embodiment shown from the back side.

This shows a magnetic force unit 500. The magnetic force unit 500 iscoupled with a base plate 75 of the dispensing head 71, and comprises acomb-shaped member driving motor 520 configured to drive, along the Yaxis direction, six comb-shaped members 51 provided with eight magnets511 on each of the front and back surfaces thereof in such a manner thatthe six comb-shaped members 51 can reciprocally move between every otheradjacent deforming element-included dispensing tip cartridge 115, arotor 530 driven to rotate by the comb-shaped member driving motor 520,and a timing belt stretched around the rotor.

Subsequently, operation of a deforming element-included dispensingdevice 100 according to an embodiment of the present invention will beexplained with reference to FIGS. 12(a) and 12(b), 13, 16, and 17.

As shown in FIG. 13, first, the deforming element-included dispensingdevice 100 has the 12 eight deforming element-included dispensing tipcartridges 115 arranged in a matrix form on the rack 220. The deformingelement-included dispensing tip cartridges 115 are loaded by engagingwith totally 24 depressed portions 221 (see FIG. 16) where the rackloading projection portions 115 a serving as the engagement unitsprovided at both ends of the arrangement direction thereof are providedon the rack 220.

In step S1, the dispensing head 71 is moved in the X axis directionusing the X axis moving mechanism 47. At this occasion, the height ofthe dispensing head 71 is controlled by the Z axis moving mechanism 48so that the support edge portions 273 provided in a protruding manner inthe inner side direction on the lower side of both side walls 271 of theframe body 270 provided with the suspension unit provided in thedispensing head 71 are located at the lower sides of the suspensionprojection portions 115 b serving as the first engagement units providedat both ends of the deforming element-included dispensing tip cartridge115 accommodated in the rack 220. It should be noted that the size ofthe both side wall 271 is formed so that the frame body 270 can coverthe series of deforming element containing portions 143 of the deformingelement-included dispensing tip cartridge 115.

In step S2, when the both side walls 271 and the upper wall 272 of theframe body 270 provided with the dispensing head 71 are located so thatthe series of deforming element containing portions of the deformingelement-included dispensing tip cartridge 115 are surrounded by itsthree surfaces, and the suspension projection portion 115 b is locatedabove the space between the adjacent projection portions 275 provided onthe support edge portion 273, the X axis moving mechanism 47 is stopped.

In step S3, when the Z axis moving mechanism 48 is controlled to movethe dispensing head 71 to the upper side, the suspension projectionportions 115 b are supported by the support edge portions 273 of theframe body 270 and the deforming element-included dispensing tipcartridge is supported by the suspension unit by its own weight.Subsequently, the Z axis moving mechanism 48 moves the frame body 270upward, so that the 12 eight deforming element-included dispensing tipcartridges 115 are moved at a time so that the inlet units 133 at thedistal ends of the narrow tube portions are located above the rack 220.

In step S4, by driving the X axis moving mechanism 47, the X axis movingbody 477 and the dispensing head 71 are located above the microplate 30.After the X axis moving body 477 is stopped, the Z axis moving mechanism48 is controlled, so that the dispensing head 71 is lowered with respectto the X axis moving body 477, and the narrow tube portion of thedeforming element-included dispensing tip 113 is inserted into each well32 of the microplate 30.

In step S5, for example, a solution in which magnetic particlescapturing DNA serving as the object substance extracted from a sample isaccommodated in each well 32 of the microplate 30 in advance. In orderto separate the object substance, the magnetic force unit 500 is drivento move the comb-shaped member 51 in the Y axis direction, so that themagnets 511 provided on the comb-shaped member 51 can come close to thenarrow tube portions of the deforming element-included dispensing tips113, and this causes the magnetic field to be given to the insidethereof. In this state, the pins 200 are moved upward and downward asshown in FIG. 12 by driving the pin driving motor to repeat the suckingand discharging of the magnetic particle suspension accommodated in thewells, so that the magnetic particles can be adsorbed to the inner wallof the narrow tube portion of each deforming element-included dispensingtip 113.

In step S6, in order to move the magnetic particles to the inside of thedeforming element-included dispensing tip 113 while the magneticparticles are still adsorbed, the Z axis moving mechanism 48 iscontrolled to move the dispensing head 71 upward from the microplate 30as shown in FIG. 17, and thereafter, the dripping prevention mechanism80 is driven, so that the dripping prevention tray 81 is moved forwardto the lower side of the deforming element-included dispensing tipcartridges 115, and the X axis moving mechanism 47 is used to move tothe required position of the microplate.

FIGS. 18A to 18D illustrate carrier-enclosed deforming element-includeddispensing tips 114, 114′, 116, 116′ having carriers enclosed thereinaccording to a fifth embodiment of the present invention. Thesecarrier-enclosed deforming element-included dispensing tips 114, 114′,116, 116′ are formed such that the area having the carriers enclosedtherein is formed separately from the main body and attached to the mainbody.

The carrier-enclosed deforming element-included dispensing tip 114 asshown in FIG. 18A comprises a tip-shaped container 154 formed with anon-deforming wall having an opening portion 144 b at an upper side andan inlet unit 134 at a lower side for allowing fluid to flow in and flowout, and a sealing plug 194 attached by engaging with the openingportion 144 b so as to seal the opening portion 144 b, and the sealingplug 194 is provided with a deforming element 124 having a deformingwall urged to shrink in the upper direction and capable of extending inthe lower direction in the tip-shaped container 154 in accordance with apressing force in the lower direction along the axis line of thetip-shaped container 154 from the outside.

The tip-shaped container 154 comprises a deforming element containingportion 144 having the opening portion 144 b and capable ofaccommodating the deforming element 124 so as to encompass a deformablerange of the deforming element 124, a narrow tube portion 184 having adiameter narrower than the deforming element containing portion 144 andhaving the inlet unit 134 that can be inserted into various kinds ofexternal containers, an accumulation portion 164 capable of accumulatingliquid sucked from the inlet unit 134 in communication with thedeforming element containing portion 144 and the narrow tube portion 184and having a diameter that is thicker than the narrow tube portion 184but is thinner than the deforming element containing portion 144, and afunnel-shaped transition unit 174′ provided between the narrow tubeportion 184 and the accumulation portion 164.

The narrow tube portion 184 has translucency, and the strip-shapedcarriers 90 are enclosed so that the carriers 90 do not flow out of thearea by processing the upper side choke portion and the lower side chokeportion for the strip-shaped carriers 90 by swaging the narrow tubeportion 184 so that the liquid can flow in and flow out but the carriers90 cannot flow out. The upper side choke portion and the lower sidechoke portion correspond to a enclosing portion.

The upper end portion of the narrow tube portion 184 is engaged with anengagement unit 174 a at the lower end of the transition unit 174, andis attached thereto by adhesion, thermal adhesion, ultrasonic adhesion,and the like. The narrow tube portion 184 is attached to the engagementunit 174 a after the carriers 90 are enclosed inside thereof. The narrowtube portion 184 corresponds to an inner portion detection area, and ispreferably formed with polypropylene that is a resin not emittingfluorescence and having a certain level of strength when the carriers 90labelled with fluorescent pigment are measured.

As the deforming element 124, the sealing plug 194 comprises a deformingwall formed with an elastic member such as rubber, and comprises atubular wall projecting to the inside of the tip-shaped container 154and comprising a bottom wall 124 a and a depression 124 c surrounded bythe side wall 124 b. Reference numeral 144 a is a bottom inlet unit ofthe deforming element containing portion 144, and is formed in a taperedmanner to become narrower toward the accumulation portion 164. Thesealing plug 194 is attached by engagement, and further, held by thehold-down plate 175 holding the sealing plug 194 from above, which makesthe attachment more rigid. The hold-down plate 175 is provided with anoperation hole 175 a provided above the deforming element 124, and isprovided with a protection wall 175 b extending in the lower directionfrom the peripheral portion of the operation hole 175 a so as to besurrounded by the deforming element 124 to prevent the deforming element124 from wearing etc. The sealing plug 194 may be attached not only byengagement but also using adhesive agent, thermal adhesion, and thelike.

In the carrier-enclosed deforming element-included dispensing tip 114′as shown in FIG. 18B, particle-like carriers 91 are enclosed instead ofthe strip-shaped carriers 90 in the narrow tube portion 184 of thecarrier-enclosed deforming element-included dispensing tip 114 explainedin FIG. 18A. The same elements as those in the carrier-encloseddeforming element-included dispensing tip 114 of FIG. 18A are denotedwith the same reference numerals, and explanation thereabout is omitted.

In the carrier-enclosed deforming element-included dispensing tip 116 asshown in FIG. 18C, a deforming element 125 is used instead of thedeforming element 124 in FIG. 18A. The deforming element 125 comprises adeforming wall formed with a flexible member, and comprises a tubularwall in a substantially circular tubular shape projecting to the insideof the tip-shaped container 154 and comprising a bottom wall 125 a and adepression 125 c surrounded by the side wall 125 b a part of which isformed with bellows. The bellows is a deforming wall disposed on aportion of the side wall 125 b of the deforming element 125 so as todivide the side wall 125 b to an upper side and a lower side andconfigured to deform in such a manner that the vertical direction is thedeforming direction. The bellows is in a screw shape, and as a wave formof the screw, crests (ten crests in this example) and roots (nine rootsin this example) are formed. The sealing plug 195 may be attached withengagement or, in addition to engagement, the sealing plug 195 may beattached with adhesion, thermal adhesion, ultrasonic adhesion, and thelike. In the case of adhesion and the like, the sealing plug 195 cannotbe detached from the tip-shaped container 154.

In the carrier-enclosed deforming element-included dispensing tip 116′as shown in FIG. 18D, particle-like carriers 91 are enclosed instead ofthe strip-shaped carriers 90 in the narrow tube portion 184 of thecarrier-enclosed deforming element-included dispensing tip 116 explainedin FIG. 18C.

FIGS. 19A to 19F illustrates carrier-enclosed deforming element-includeddispensing tips 117, 117′, 118, 118′, 119, 119′ in which carriersaccording to another example of the fifth embodiment of the presentinvention are enclosed. These carrier-enclosed deformingelement-included dispensing tips 117, 117′, 118, 118′, 119, 119′ areformed such that the area in which the carriers are enclosed is formedintegrally with the main body.

The carrier-enclosed deforming element-included dispensing tip 117 asshown in FIG. 19A comprises a tip-shaped container 155 formed with anon-deforming wall having an opening portion 145 b at an upper side andan inlet unit 135 at a lower side for allowing fluid to flow in and flowout, and a sealing plug 196 attached by engaging with the openingportion 145 b so as to seal the opening portion 145 b, and the sealingplug 196 is provided with a deforming element 126 having a deformingwall urged to shrink in the upper direction and capable of extending inthe lower direction in the tip-shaped container 155 in accordance with apressing force in the lower direction along the axis line of thetip-shaped container 155 from the outside.

The tip-shaped container 155 comprises a deforming element containingportion 145 having the opening portion 145 b and capable ofaccommodating the deforming element 126 so as to encompass a deformablerange of the deforming element 126, a narrow tube portion 185 incommunication with the deforming element containing portion 145 andhaving a diameter narrower than the deforming element containing portion145 and having the inlet unit 135 that can be inserted into variouskinds of external containers, and a transition unit 145 a disposedbetween the narrow tube portion 185 and the deforming element containingportion 145.

The narrow tube portion 185 has translucency, and the strip-shapedcarriers 90 are enclosed so that the carriers 90 do not flow out of thearea by processing the upper side choke portion and the lower side chokeportion for the strip-shaped carriers 90 by swaging the narrow tubeportion 184 so that the liquid can flow in and flow out but the carriers90 cannot flow out. The upper side choke portion and the lower sidechoke portion correspond to a enclosing portion. The narrow tube portion185 corresponds to the inner portion detection area.

As the deforming element 126, the sealing plug 196 comprises a deformingwall formed with an elastic member such as rubber, and comprises atubular wall projecting to the inside of the tip-shaped container 155and comprising a bottom wall 126 a and a depression 126 c surrounded bythe side wall 126 b. Reference numeral 145 a is a bottom inlet unit ofthe deforming element containing portion 145, and is formed in a taperedmanner to become narrower toward the narrow tube portion 185. Thesealing plug 196 may be attached with engagement or, in addition toengagement, the sealing plug 196 may be attached with adhesion, thermaladhesion, ultrasonic adhesion, and the like. In the case of adhesion andthe like, the sealing plug 196 may be attached with not only adhesion,but also thermal adhesion, ultrasonic adhesion, and the like. In thesecases, the sealing plug 196 cannot be detached from the tip-shapedcontainer 155. When the sealing plug 196 is attached, the hold-downplate 177 holding the sealing plug 196 from above is attached, whichmakes the attachment more rigid. The hold-down plate 177 is providedwith an operation hole 177 a provided above the deforming element 126,and is provided with a protection wall 177 b extending in the lowerdirection from the peripheral portion of the operation hole 177 a so asto be surrounded by the deforming element 126.

In the carrier-enclosed deforming element-included dispensing tip 117′as shown in FIG. 19B, particle-like carriers 91 are enclosed instead ofthe strip-shaped carriers 90 in the narrow tube portion 185 of thecarrier-enclosed deforming element-included dispensing tip 117 explainedin FIG. 19A.

The carrier-enclosed deforming element-included dispensing tip 118 asshown in FIG. 19C comprises a tip-shaped container 155 formed with anon-deforming wall having an opening portion 146 b at an upper side andan inlet unit 136 at a lower side for allowing fluid to flow in and flowout, and a sealing plug 196 adhered, using an adhesive agent and thelike, and engaging with the opening portion 146 b to be attached theretoso as to seal the opening portion 146 b, and the sealing plug 196 isprovided with a deforming element 126 having a deforming wall urged toshrink in the upper direction and capable of extending in the lowerdirection in the tip-shaped container 156 in accordance with a pressingforce in the lower direction along the axis line of the tip-shapedcontainer 156 from the outside.

The tip-shaped container 156 comprises a deforming element containingportion 146 having the opening portion 146 b and capable ofaccommodating the deforming element 126 so as to encompass a deformablerange of the deforming element 126, a narrow tube portion 186 having adiameter narrower than the deforming element containing portion 146 andhaving the inlet unit 136 that can be inserted into various kinds ofexternal containers, an accumulation portion 165 capable of accumulatingliquid sucked from the inlet unit 136 in communication with thedeforming element containing portion 146 and the narrow tube portion 186and having a diameter that is thicker than the narrow tube portion 186but is thinner than the deforming element containing portion 146, and afunnel-shaped transition unit 176 provided between the narrow tubeportion 186 and the accumulation portion 165.

The accumulation portion 165 has translucency, and multiple cubiccarriers 92 having diameters larger than the internal diameter of thenarrow tube portion 186 and capable of capturing a predeterminedsubstance by adsorption and the like to serve as a particle-like fillingagent for chromatography are enclosed in the accumulation portion 165.The transition unit 176 has an elliptic shape in a cross sectionperpendicular to the axis direction, so that the transition unit 176 isnot blocked by the cubic carriers 92. In this case, the “filling agent”is an insoluble stationary phase filled in a selected predeterminedcontainer in order to adsorb an object biological material included in apredetermined fluid serving as a so-called mobile phase on the basis ofthe principle of liquid chromatography.

In the carrier-enclosed deforming element-included dispensing tip 119 asshown in FIG. 19D, a deforming element 127 is used instead of thedeforming element 126 in FIG. 19A. The deforming element 127 comprises adeforming wall formed with a flexible member, and comprises a tubularwall in a substantially circular tubular shape projecting to the insideof the tip-shaped container 155 and comprising a bottom wall 127 a and adepression 127 c surrounded by the side wall 127 b a part of which isformed with bellows. The bellows is a deforming wall disposed on aportion of the side wall 127 b of the deforming element 127 so as todivide the side wall 127 b to an upper side and a lower side andconfigured to deform in such a manner that the vertical direction is thedeforming direction. The bellows is in a screw shape, and as a wave formof a screw, crests (ten crests in this example) and roots (nine roots inthis example) are formed.

In the carrier-enclosed deforming element-included dispensing tip 119′as shown in FIG. 19E, particle-like carriers 91 are enclosed instead ofthe strip-shaped carriers 90 in the narrow tube portion 185 of thecarrier-enclosed deforming element-included dispensing tip 119 explainedin FIG. 19D.

In the carrier-enclosed flat-shaped element-included dispensing tip 118′as shown in FIG. 19F, the deforming element 127 is used instead of thedeforming element 126 of the carrier-enclosed deforming element-includeddispensing tip 118 explained in FIG. 19C.

In FIGS. 18A to 18D and 19A to 19F, reference numerals 114 a, 117 a, 118a denote suspension projection portions for suspending the tip from adispensing tip head and the like.

Although not shown in the drawings, the carrier-enclosed deformingelement-included dispensing tip can be of course integrated like thedeforming element-included dispensing tip cartridge.

In order to measure the optical state in the carrier-enclosed deformingelement-included dispensing tip, for example, the carrier-encloseddeforming element-included dispensing tip is provided in the dispensinghead, and by using the light detection unit provided with the dispensinghead, the optical state in the tip is measured by using one or morelight reception terminals disposed in proximity to surround theperiphery of the non-deforming portion at the outside of eachcarrier-enclosed deforming element-included dispensing tip. At thisoccasion, the light reception terminal is preferably movable relativelywith respect to the tip.

Device examples will be shown in FIGS. 20(a), 20(b), 21(a), and 21(b) assuch examples.

FIGS. 20A and 20B illustrate examples of a light detection unit 88 andmagnetic force units 501, 502 according to the fifth embodiment usedinstead of the magnetic force units 50, 500 used with the deformingelement-included dispensing devices 10, 100 suitable for a case wherecarrier-enclosed deforming element-included dispensing tips 114, 114′,116, 116′, 117, 117′, 118, 118′, 119, 119′ are used.

FIG. 20A is a perspective view illustrating only the magnetic force unit501 and the light detection unit 88. The magnetic force unit 501comprises three substantially square pillar-shaped comb-shaped members521 which are as many as (the number of columns−1) of thecarrier-enclosed deforming element-included tips and which are providedto be movable along the column direction between the adjacent columns ofthe carrier-enclosed deforming element-included dispensing tips having acolumn interval configured to be, e.g., twice a natural number of acolumn interval of the wells 32, i.e., a column interval configured tobe “twice” and are provided to have such a width that the substantiallysquare pillar-shaped comb-shaped members 521 extend along the columndirection and can be inserted between adjacent columns of thecarrier-enclosed deforming element-included dispensing tips, twosubstantially square pillar-shaped comb-shaped ends 521 a, 521 bprovided outside of the comb-shaped member 521 and formed so as toslightly wider than the comb-shaped member 521, and a support member(not shown) coupled with one end of the comb-shaped member 521 and thecomb-shaped ends 521 a, 521 b and extending in the row direction, andeach of the comb-shaped members 521 and the comb-shaped end 521 bcomprises magnets 522 as many as the number of rows (12 magnets 522)with an interval configured to be the row interval of the wells 32 alongthe longitudinal direction, i.e., the column direction, and a guide rail523 provided along the longitudinal direction, i.e., the columndirection, of each of the comb-shaped members 521, 521 a, 521 b. Themagnet 522 is provided at the same side surface side as the comb-shapedmember 521 and the comb-shaped end 521 b, and the guide rail 523 isprovided at a position far from the side surface. The guide rail 523guides the movement of the comb-shaped light detection unit 88 providedto be movable on the upper surfaces of the comb-shaped members 521, 521a, 521 b. In this case, for example, the column interval or the rowinterval of adjacent carrier-enclosed deforming element-includeddispensing tips are configured to be “twice” the column or row intervalof the wells 32, but it is to be understood that they can be set to thesame interval. In this case, it is to be understood that the number ofcomb-shaped members also change in accordance with the number ofintervals and how the magnets and light detection holes explained laterare arranged.

FIG. 20B is a perspective view illustrating an example of the magneticforce unit 502 and the light detection unit 88 according to anotherexample of the fifth embodiment.

FIGS. 21A and 21B illustrate the details of the light detection unit 88,and the light detection unit 88 is provided to be movable relativelywith respect to the magnetic force units 501, 502 on the magnetic forceunits 501, 502 provided with the dispensing heads 70, 71, and isconfigured to detect the state of the inside of each carrier-encloseddeforming element-included dispensing tip.

The light detection unit 88 comprises three substantially squarepillar-shaped comb-shaped members 95 which are as many as (the number ofcolumns−1) of the carrier-enclosed deforming element-included dispensingtips and which are provided to be movable with respect to the magneticforce units 501, 502 or the carrier-enclosed deforming element-includedtip along the column direction between the adjacent carrier-encloseddeforming element-included tips having a column interval configured tobe, e.g., twice a natural number of a column interval of the wells 32,i.e., a column interval configured to be “twice” and are provided tohave such a width that the substantially square pillar-shapedcomb-shaped members 95 extend along the column direction and can beinserted between adjacent columns of the carrier-enclosed deformingelement-included dispensing tips, two substantially square pillar-shapedcomb-shaped ends 95 a, 95 b provided outside of the comb-shaped member95 and formed so as to slightly wider than the comb-shaped member 95,and a support member 96 coupled with one end of the comb-shaped member95 and the comb-shaped ends 95 a, 95 b and extending in the rowdirection, and each of the comb-shaped members 95 and the comb-shapedends 95 a, 95 b is provided with a light detection hole 98 penetratingand arranged along the row direction.

The light detection hole 98 provided on each of the comb-shaped members95 and the comb-shaped ends 95 a, 95 b is provided with a distal end ofthe optical fiber 99 extending from the light emission unit 103, and thelight detection hole 98 of an adjacent comb-shaped member 95 or thecomb-shaped end 95 a, 95 b with a narrow and long gap interposedtherebetween where the column of the carrier-enclosed deformingelement-included dispensing tip is to be disposed is provided so thatthe distal end of the optical fiber 101 connected with the light sensor102 faces the gap sandwiched by the comb-shaped members 95 or the twocomb-shaped ends 95 a, 95 b adjacent to each other.

It should be noted that reference numeral 97 denotes a narrow grooveprovided with each of the comb-shaped members 95 and the comb-shapedends 95 a, 95 b along the column direction engaging with and capable ofsliding on the guide rail 523. The sizes and the shapes of thecomb-shaped members 95 and the comb-shaped ends 95 a, 95 b and thesupport member 96 of the light detection unit 88 are respectively formedin sizes and shapes corresponding to the magnetic force units 501, 502.

Each of the embodiments explained above is to explain the presentinvention in a specific manner so that the present invention isunderstood more clearly, and each of the embodiments explained abovedoes not limit other embodiments. Therefore, the embodiments can bechanged without changing the gist of the invention. For example, in theembodiment, the volumes use ranges of volumes, i.e., a small volume(several dozen to 200 microliters), a medium volume (200 microliters to1 milliliter), and a large volume (1 to 5 milliliters), but they are allexamples, and the volume is not limited to each range. In order to drivethe movable member, the movable member is directly driven using thelinear step motor, but further, one end thereof may be axiallysupported, and the other end thereof may be driven using a link stickhaving a fulcrum at the intermediate point and driven in the verticaldirection by a linear motor, or may be driven using a step motor and cammechanism.

In the embodiment, an example where a tip arrangement holding unit isused in the tip support portion has been explained. However, if, withrespect to the tray 22 corresponding to the tip arrangement holdingunit, each deforming element-included dispensing tip 11 is considered tobe integrally attached to the tray 22, this means that an example of adeforming element-included dispensing tip cartridge has been shown.

The shape of the deforming element-included dispensing tip is notlimited to what has been described above, but the shape of the deformingelement-included dispensing tip may have a step in the transition unit,or may have a step in a portion other than the transition unit.

The tip arrangement holding unit is not limited to an arrangement of amatrix form of 12 rows×8 columns explained above. For example, there arelinear arrangements such as 4, 6, 8, 12 lines, and the like, or a matrixform with 24, 48, 384 lines, and the like, and arrangements of othershapes.

The deforming element-included dispensing tip cartridge has beenexplained in a case of only eight lines, but is not limited thereto. Forexample, linear arrangements such as 4, 6, 12 lines, or deformingelement-included dispensing tip cartridges are coupled with each other,and for example, there may be an arrangement in a matrix form of 12rows×8 columns and the like.

The example of movement in the X axis and the Z axis has been explained,but it is to be understood that movement in the Y axis can also beadded.

Further, the inlet unit of the narrow tube portion of the deformingelement-included dispensing tip may be engaged with a short tube ofwhich diameter is narrower such as those made of stainless and the like,so that the dispensing precision is enhanced.

In the above explanation, only the strip-shaped carriers, theparticles-shaped carriers, and the cubic carriers have been explained ascarriers. However, the embodiment is not limited to these carriers orthe number thereof, and for example, block-shaped carriers, a single cubcarrier, other numbers of particle-like carriers can be used.

The enclosing portion has been explained only in the case of swaging,but the embodiment is not limited thereto, and, for example, theprojection portions protruding in the inner side direction and theenclosing portion formed separately can be used.

Expressions in terms of space explained above such as “upper side”,“lower side”, “bottom”, “inside”, “outside”, “row”, “column”, “X”, “Y”,“Z”, and the like used in the above explanation are given only for thedrawings, and it is understood that these expressions do not limit theembodiments to a particular special direction or arrangement of thestructure.

The above constituent elements, components, devices, and the like, forexample, the tip-shaped container, the deforming element, the narrowtube portion, the accumulation portion, the container, the dispensinghead, the sealing plug, the hold-down plate, the deformingelement-included dispensing tip, the deforming element-includeddispensing tip cartridge, the movable member, the magnetic force means,the movement mechanism, the carriers of the particle-like carrier, thestrip-shaped carrier, and the like (the carriers are not limitedthereto), enclosing portion, and the like may be combined in any waywhile deforming as appropriately.

INDUSTRIAL APPLICABILITY

The deforming element-included dispensing tip, the deformingelement-included dispensing device, and the deforming element-includeddispensing processing method according to the present invention arerelated to fields requiring processing of various kinds of solutions,for example, various kinds of fields such as industrial fields, food,agricultural, agriculture fields such as fish processing, pharmaceuticalfields, medical field dealing with health, insurance, immunity, disease,genetic, and the like, fields such as chemical or biology. Inparticular, the present invention is effective in a case of sequentiallyexecuting a series of processing using many reagents and substances withprocessing in a predetermined order.

REFERENCE SIGNS LIST

-   -   10, 100 deforming element-included dispensing device    -   11, 11′, 110, 111, 112, 113 deforming element-included        dispensing tip    -   115 deforming element-included dispensing tip cartridge    -   114, 116, 117, 118, 119 carrier-enclosed deforming        element-included dispensing tip    -   12, 120, 121, 122, 123, 124, 125, 126, 127 deforming element    -   15, 150, 151, 152, 153, 154, 155 tip-shaped container    -   20, 200 pin (movable member)    -   30 microplate    -   50, 500, 501, 502 magnetic force unit    -   70, 71 dispensing head    -   88 light detection unit    -   90, 91, 92 carrier

1. A deforming element-included dispensing tip comprising: a tip-shapedcontainer formed with a non-deforming wall having an opening portion atan upper side and an inlet unit at a lower side for allowing fluid toflow in and flow out, the non-deforming wall defining an area capable ofaccommodating fluid, wherein the area capable of accommodating fluid islocated between the opening portion and the inlet unit; and a sealingplug attached to the opening portion so as to seal the opening portion,wherein the sealing plug comprises a deforming element that is locatedinside the tip-shaped container, and that has a tubular deforming wallthat is formed so as to be able to extend in a lower direction in thetip-shaped container in accordance with a pressing force from an outsideand is formed so as to be urged to shrink or be able to shrink in anupper direction, wherein the sealing plug has a depression surrounded bythe tubular deforming wall, wherein the tubular deforming wall comprisesa bottom wall on which the pressing force is exerted from the outside toextend the deforming element in the lower direction, and furthercomprises a side wall extending upward from the bottom wall, wherein anannular space is sandwiched between: the side wall of the tubulardeforming wall, and the non-deforming wall of the tip-shaped container,and wherein the annular space is configured to be in fluid communicationwith the area capable of accommodating fluid in the tip-shapedcontainer.
 2. A deforming element-included dispensing tip according toclaim 1, wherein the tip-shaped container comprises a deforming elementcontaining portion having the opening portion and capable of receivingthe deforming element so as to encompass a deformable range of thedeforming element, and a narrow tube portion formed so as to be narrowerthan the deforming element containing portion and having the inlet unit.3. (canceled)
 4. The deforming element-included dispensing tip accordingto claim 1, comprising a hold-down plate attached to the tip-shapedcontainer at the upper side of the sealing plug and holding the sealingplug from the upper side, and the hold-down plate is provided with anoperation hole, and a protection wall formed so as to extend in thelower direction from the peripheral portion of the operation hole so asto be surrounded by the deforming element.
 5. The deformingelement-included dispensing tip according to claim 1, wherein the sidewall of the tubular deforming wall comprises a flexible member, and isformed with bellows.
 6. The deforming element-included dispensing tipaccording to claim 1, wherein the side wall of the tubular deformingwall has an elastic member.
 7. The deforming element-included dispensingtip according to claim 1, wherein the sealing plug has an elasticmember, and is attached to the opening portion of the tip-shapedcontainer by using an O ring.
 8. The deforming element-includeddispensing tip according to claim 1, wherein a carrier capable of cominginto contact with a fluid flowing in and out through the inlet unit andbonded with or capable of being bonded with a predetermined substance isenclosed in the tip-shaped container.
 9. A deforming element-includeddispensing tip cartridge, comprising: a plurality of tip-shapedcontainers formed with a non-deforming wall so as to be integrallycoupled and provided with a plurality of opening portions at an upperside and provided with a plurality of inlet units at a lower side forallowing fluid to flow in and flow out, each of the tip-shapedcontainers defining an area capable of accommodating fluid, wherein thearea capable of accommodating fluid is located between a respective oneof the opening portions and the inlet unit corresponding to therespective one of the opening portions; and a plurality of sealing plugsattached to the opening portions so as to seal the opening portions,wherein each of the sealing plugs comprises a deforming element that islocated inside a respective one of the tip-shaped containers, and thathas a tubular deforming wall that is formed so as to be able to extendin a lower direction in the respective one of the tip-shaped containersin accordance with a pressing force from an outside and is formed so asto be urged to shrink or so as to be able to shrink in an upperdirection, wherein each of the sealing plugs has a depression surroundedby the corresponding tubular deforming wall, wherein each of the tubulardeforming walls comprises a bottom wall on which the pressing force isexerted from the outside to extend the deforming element, and furthercomprises a side wall extending upward from the bottom wall, wherein anannular space is sandwiched between the side wall of the tubulardeforming wall and the non-deforming wall of the correspondingtip-shaped container, and wherein the annular space is configured to bein fluid communication with the area capable of accommodating fluid inthe corresponding tip-shaped container.
 10. The deformingelement-included dispensing tip cartridge according to claim 9, whereineach of the tip-shaped containers comprises a deforming elementcontaining portion having the opening portion and capable of receivingthe deforming element so as to encompass a deformable range of thedeforming element, and a narrow tube portion formed so as to be narrowerthan the deforming element containing portion and having the inlet unit.11. (canceled)
 12. The deforming element-included dispensing tipcartridge according to claim 9, comprising a hold-down plate attached tothe tip-shaped containers at the upper side of the sealing plugs andholding the sealing plugs from the upper side, and the hold-down plateis provided with an operation hole in association with each of thesealing plugs, and a protection wall formed so as to extend in the lowerdirection from the peripheral portion of the operation hole and so as tobe surrounded by the deforming element.
 13. The deformingelement-included dispensing tip cartridge according to claim 9, whereinthe deforming element-included dispensing tip cartridge is provided withtwo engagement units which are a first engagement unit and a secondengagement unit which are provided in a projecting manner or in arecessed manner with respect to an external direction at both ends alongthe arrangement direction thereof, and the first engagement unit isdisposed at a first height, and the second engagement unit is disposedat a second height lower than the first height.
 14. The deformingelement-included dispensing tip cartridge according to claim 9, whereinin a state of capable of coming into contact with a fluid that flows inand out through the inlet unit, a carrier bonded with or capable ofbeing bonded with a predetermined substance is enclosed in an innerportion detection area which is inside of the tip-shaped container.15-36. (canceled)